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Nox3 might serve as a molecular target for the development of therapeutics for sensorineural hearing loss

CATEGORY:
Research

SCREENSHOT:
Nox3-derived superoxide in cochleae induces sensorineural hearing loss Mechanisms of Nox3-dependent hearing loss

TITLE:
Nox3-derived superoxide in cochleae induces sensorineural hearing loss Mechanisms of Nox3-dependent hearing loss

CONTENT:
J Neurosci. 2021 Apr 13:JN-RM-2672-20. doi: 10.1523/JNEUROSCI.2672-20.2021. Online ahead of print.

ABSTRACT

Reactive oxygen species (ROS) produced by NADPH oxidases (Nox) contribute to the development of different types of sensorineural hearing loss (SNHL), a common impairment in humans with no established treatment. Although the essential role of Nox3 in otoconia biosynthesis and its possible involvement in hearing have been reported in rodents, immunohistological methods targeted at detecting Nox3 expression in inner ear cells reveal ambiguous results. Therefore, the mechanism underlying Nox3 -dependent SNHL remains unclear and warrants further investigation. We generated Nox3-Cre knock-in mice, in which Nox3 was replaced with Cre recombinase (Cre ). Using Nox3-Cre;tdTomato mice of either sex, in which tdTomato is expressed under the control of the Nox3 promoter, we determined Nox3-expressing regions and cell types in the inner ear. Nox3 -expressing cells in the cochlea included various types of supporting cells (SC), outer hair cells (OHC), inner hair cells (IHC), and spiral ganglion neurons (SGN). Nox3 expression increased with cisplatin, age, and noise insults. Moreover, increased Nox3 expression in SC and OHC, especially at the basal turn of the cochlea, played essential roles in ROS-related SNHL. The extent of Nox3 involvement in SNHL follows the following order: cisplatin-induced HL (CIHL) > age-related HL (ARHL) > noise-induced HL (NIHL). Here, on the basis of Nox3-Cre;tdTomato , which can be used as a reporter system (Nox3-Cre+/- ;tdTomato+/+ and Nox3-Cre+/+ ;tdTomato+/+ ), and Nox3 -KO (Nox3-Cre+/+ ;tdTomato+/+ ) mice, we demonstrate that Nox3 inhibition in the cochlea is a promising strategy for ROS-related SNHL, such as CIHL, ARHL, and NIHL.SIGNIFICANCE STATEMENT: We found Nox3-expressing regions and cell-types in the inner ear, especially in the cochlea, using Nox3-Cre;tdTomato mice, a reporter system generated in this study. Nox3 expression increased with cisplatin, age, and noise insults in specific cell-types in the cochlea and resulted in the loss (apoptosis) of outer hair cells. Thus, Nox3 might serve as a molecular target for the development of therapeutics for sensorineural hearing loss, particularly cisplatin-induced, age-related, and noise-induced hearing loss.

PMID:33849947 | DOI:10.1523/JNEUROSCI.2672-20.2021

SOURCE:
The Journal of neuroscience : the official journal of the Society for Neuroscience

PUBLISHER:

PMID:
pubmed:33849947

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33849947

DOI:
10.1523/JNEUROSCI.2672-20.2021

DATE – PUBLISHED:
Wed, 14 Apr 2021 06:00:00 -0400

DATE – DOI:
2021-04-13T18:12:49Z

DATE – ADDED:
04/14/21 09:45AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33849947/

LINK – DOI:
https://doi.org/10.1523/JNEUROSCI.2672-20.2021

LINK – PUBLISHER:
http://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.2672-20.2021?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-04-14T13:45:44+00:00, https://www.hearinglosstreatmentreport.com.

PBM/NAC treatment may reduce hair cell loss associated with noise-induced hearing loss

PBM/NAC treatment may prevent hearing dysfunction caused by NIHL

CATEGORY:
Research

SCREENSHOT:
Combination photobiomodulation/N-acetyl-L-cysteine treatment appears to mitigate hair cell loss associated with noise-induced hearing loss in rats

TITLE:
Combination photobiomodulation/N-acetyl-L-cysteine treatment appears to mitigate hair cell loss associated with noise-induced hearing loss in rats

CONTENT:
Lasers Med Sci. 2021 Apr 6. doi: 10.1007/s10103-021-03304-2. Online ahead of print.

ABSTRACT

Sensorineural hearing loss is an intractable disease. Acoustic overstimulation creates hearing loss; many patients exhibit social and emotional dysfunctions. In a model of noise-induced hearing loss (NIHL), low-level laser photobiomodulation (PBM) at a near-infrared wavelength significantly improved auditory brainstem response (ABR) thresholds. In addition, both N-acetyl-L-cysteine (NAC) and acetyl-L-carnitine (ALCAR) attenuated NIHL, reducing the effects of noise trauma in the cochlea and the central auditory system. Here, we combined PBM with antioxidants to explore hearing threshold recovery and morphological hair cell changes after rats were exposed to noise. The average auditory brainstem response thresholds after PBM/NAC combination treatment were reduced from the apex to the basal turn at all of 8, 16, and 32 kHz compared to the noise-only group. The PBM/NAC combination treated group exhibited intact outer hair cells in all turns, and significantly greater hair cell numbers in the middle and basal cochlear turns, than did controls. Thus, PBM/NAC treatment may prevent hearing dysfunction caused by NIHL.

PMID:33822307 | DOI:10.1007/s10103-021-03304-2

SOURCE:
Lasers in medical science

PUBLISHER:

PMID:
pubmed:33822307

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33822307

DOI:
10.1007/s10103-021-03304-2

DATE – PUBLISHED:
Tue, 06 Apr 2021 06:00:00 -0400

DATE – DOI:
2021-04-06T07:04:00Z

DATE – ADDED:
04/06/21 07:30PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33822307/

LINK – DOI:
https://doi.org/10.1007/s10103-021-03304-2

LINK – PUBLISHER:
http://link.springer.com/10.1007/s10103-021-03304-2?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-04-06T23:30:28+00:00, https://www.hearinglosstreatmentreport.com.

NLRP3 inhibitors such as Oridonin may provide new treatment strategy for noise-induced hearing loss

Some research that appeared on our radar recently: “Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 – NEK7 mediated inflammasome activation” (March 23, 2021).

Link to the paper:

https://www.sciencedirect.com/science/article/pii/S1567576921002125

Excerpt:

Here, we further determined that treatment with oridonin could indeed interrupt the interaction between NLRP3 and NEK7 as well as inhibit the downstream inflammasome activation in mouse cochleae after noise exposure. Furthermore, we tested anakinra, another inflammatory inhibitor, and it was shown to partially alleviate the degree of hearing impairment in some frequencies in an NIHL mouse model. These discoveries suggest that inhibiting NLRP3 inflammasomes and the downstream signaling pathway may provide a new strategy for the clinical treatment of NIHL.

see it's simple toy story meme hearing loss oridoninWhat does that mean?

Here is an extremely loose – but simple – explanation of what this means:

  • inflammation is involved in noise-induced hearing loss (NIHL)
  • we aren’t sure how, exactly
  • but it seems that… sometimes… inflammation can go way too far
  • which might actually make things worse, or interfere with healing
  • this could be what happens in the ear after acoustic trauma
  • we aren’t sure about that either
  • but according to this theory…
  • maybe a drug that keeps the inflammation process from going way too far…
  • … might also help with the healing process and prevent further damage
  • (by making sure inflammation does not get carried away)
  • this might apply in the context of noise-induced hearing loss
  • Oridonin, anakinra are two drugs worth studying for this
  • but we aren’t sure… yet

Now, for those of you who prefer the nitty gritty details… diving deep into the science… and the technical side of things…

Here is some further reading about Oridonin – “a covalent NLRP3 inhibitor with strong anti-inflammasome activity” – from Nature:

https://www.nature.com/articles/s41467-018-04947-6

From that paper:

Oridonin (Ori) is the major active ingredient of the traditional Chinese medicinal herb Rabdosia rubescens and has anti-inflammatory activity, but the target of Ori remains unknown. NLRP3 is a central component of NLRP3 inflammasome and has been involved in a wide variety of chronic inflammation-driven human diseases.

Hmmm…

(I wonder if it has anything to do with osteoclasts…)

That’s all for now.

PS: I am finally finishing the setup for email updates. If you have already signed up for the newsletter… in the next few days you will (finally) be getting an email from newsleter@hearinglosstreatmentreport.com asking you to confirm your email address. First issue of the official Hearing Loss Treatment Report Newsletter is going to be a very special one… – Michael (author/admin)

Estimated PIPE-505 Phase 2a Study Completion Date: June 12, 2021

Short but sweet update:

We now have an estimated completion date for the PIPE-505 phase 2a clinical trial: June 12, 2021.

Details below:

  • The PIPE-505 study record was updated on March 29, 2021.
  • The study completion date was changed from March 2021 [Anticipated] to June 2021 [Anticipated].
  • The June 12, 2021 date [Estimated] was calculated using information found within the study record and its history of changes, including: a) the submission date on which the Study Status was changed from “Recruiting” to “Active, not recruiting” and, b) the maximum follow-up Time Frame (“3 months after drug administration”) as detailed in the Outcome Measures section.
  • For a more conservative completion date, replace the last submitted update to Study Status date with the more recent last submitted update date of March 26, 2021. This gives us June 24, 2021.
  • Taken together, we are looking at a range of June 12 – June 24, with June 12th as the one to mark on your calendar.

PIPE-505 phase 2 completion date

Source: History of Changes for Study: NCT04462198 (Phase I/IIa Study Evaluating Safety and Efficacy of an Intratympanic Dose of PIPE-505 in Subjects With Hearing Loss)

That’s all for now.

We will probably have the next PIPE-505 update for you before June 15th (and/or whenever Pipeline Therapeutics makes an announcement).

For ongoing PIPE-505 updates and news of other upcoming hearing loss treatments, sign up for the free once-weekly email newsletter.

Message from the author:

Hey, Michael here. Thanks for visiting and… feel free to email michael@urgentresearch.com and say hello, any time. Let me know what type of hearing restoration treatment updates you want. Or tell me which experimental treatments you’re following closely right now. Feedback is also welcome and reader questions are encouraged.

P.S. Small favor to ask. Do you know someone who might find the information on this website helpful or uplifting? If you do… would you send them a link? Here: https://www.hearinglosstreatmentreport.com/

Sincerely,
Michael

BREAKING: CGF166 Clinical Trial Results Posted Online…

CGF166 update: Results from the phase 1/2 study of the hearing loss drug are now available.

Developing story…

CGF166 has results clinical trial update

Two days ago, on March 30, 2021, the official study record of CGF166 was updated on ClinicalTrials.gov.

This update was not accompanied by a press release from Novartis nor any media coverage.

However, this “surprise” update had two important words: has results.

An unexpected update

These results came out of nowhere…

For anyone learning about CGF166 for the first time, here is some quick background info on the “mysterious” Novartis gene therapy drug candidate for hearing loss:

A Case Study: Using Regenerative Medicine to Treat Hearing Loss

In 1999, scientists singled out a gene called atonal as a “master switch” for turning on the growth of inner ear hair cells, which pick up sound waves and translate them into electrical signals in the brain. Humans are born with hair cells, but the atonal switch flips off at birth. Any subsequent damage to hair cells is permanent.

In collaboration with a biotech company, GenVec Inc, NIBR researchers have developed an experimental gene therapy called CGF166 to restore hearing function by regenerating hair cells. It consists of a viral vector carrying the atonal gene. The vector has been altered with the aim of making it harmless and is injected directly into the inner ear. CGF166 is now being tested in a limited number of patients with severe-to-profound hearing loss.

SOURCE: an old brochure from the Novartis Institute for Biological Research (NIBR), circa 2016.

Sounds promising, right?

Absolutely.

But that material was written 5 years ago and… since then – aside from the early buzz and media coverage on this holy grail treatment – CGF166 updates have been incredibly rare.

In fact, before today… the last credible update we got on CGF166 was from over a year ago when, on February 21, 2020, BioCentury pointed out that Novartis had “yet to publicly report data from its Phase I/II trial of gene therapy CGF166.”

SOURCE: Regenerative medicine for hearing loss makes quiet progress, BioCentury, https://www.biocentury.com/article/304491, dated February 21, 2020.

Well, now it looks like they (quietly) have.

The results were uploaded to the study record of the phase I/II clinical trial. Here is the official description:

The goal of the study was to evaluate the safety, tolerability, and the potential ability of CGF166 delivered through IL-infusion to improve hearing. CGF166 is a recombinant adenovirus 5 (Ad5) vector containing a cDNA encoding the human Atonal transcription factor (Hath1).

This study evaluated the safety, tolerability, and potential efficacy of CGF166 and the associated delivery procedures in patients with severe-to-profound unilateral or bilateral hearing loss. Eligible patients were required to have documented, non-fluctuating hearing loss.

SOURCE: https://clinicaltrials.gov/ct2/show/NCT02132130, last updated March 30, 2021.

CGF166 study results: Part 1

These results do not show all the data and numbers, but we expect to post a follow-up once we have some experts review them.

Here is the direct link to the study results that were uploaded on March 30, 2021: ClinicalTrials.gov Identifier: NCT02132130 – Study Results

It’s important to keep in mind that these results are NOT the same thing as an announcement or press release from the company. For that reason, there is no accompanying commentary or explanation of what these results mean.

CGF166 results sneak preview confusion emojiThis can be frustrating, but here at Hearing Loss Treatment Report we are currently working on a follow-up post that will provide a clear idea of what these numbers mean for people with hearing loss.

This is a developing story…

I wish we had more for you.

This is all we have, for now.

We will continue to monitor what is happening with CGF166 and post an update as soon as we know more. (The best way to get updates is by subscribing to our email newsletter – which we’ll be sending out very soon!)

cgf166 trial results meme

For now, we decided to share the link to these “raw” results because we believe in sharing early and sharing often. Information ASAP. Before the official press releases, before company Twitter announcements, before the media outlets, before before before.

And so, for that reason, we didn’t want to sit and wait on this long-awaited study result update just so we could organize it into a neatly-wrapped package with in-depth commentary.

That’s not our style.

“First”

The reason we believe in this post-first-question-later approach is because an increasingly large number of patients, organizations, and industry professionals use this site as a shortcut to the very latest hearing loss treatment updates.

Think of this site like a secret source of some of the fastest, earliest updates in the world of hearing loss drug development. And it’s meant to help inform people in situations like this: where this CGF166 phase I/II results story was missed, ignored, or simply too early (and thus unknown) to the mainstream media.

Which is also why you might want to subscribe to our email updates list… so you can get as-fast-as-we-can-find-them updates on experimental hearing restoration drugs and milestones… plus, sneak previews of what potential “cures” are really around the corner in 2021, 2022, and beyond…

But it’s not for everyone.

Questions? Comments? Corrections? Feedback:

Send an email to michael@urgentresearch.com and say hello.

Protective effects of vitamins/antioxidants on occupational noise-induced hearing loss: A systematic review

CATEGORY:
Research

SCREENSHOT:
Protective effects of vitamins/antioxidants on occupational noise-induced hearing loss: A systematic review

TITLE:
Protective effects of vitamins/antioxidants on occupational noise-induced hearing loss: A systematic review

CONTENT:
J Occup Health. 2021 Jan;63(1):e12217. doi: 10.1002/1348-9585.12217.

ABSTRACT

OBJECTIVES: Occupational noise-induced hearing loss (NIHL) due to industrial, military, and other job -related noise exposure can cause harmful health issues to occupied workers, but may also be potentially preventable. Vitamins/antioxidant have been studied as therapeutic strategies to prevent and/or delay the risks of human diseases as well as NIHL .So, this study was conducted to systematically review the protective effects of vitamins/antioxidants on occupational NIHL.

METHODS: Online databases including PubMed/Medline, Scopus, Web of Science, EMBASE, Science Direct, and Google Scholar were systematically searched up to 12 January 2021. Based on 6336 potentially relevant records identified through the initial search in the databases, 12 full-text publications were retrieved, one of which can be viewed as two separate trials, because it has studied the effects of two different antioxidants (ginseng and NAC) on NIHL, separately.

RESULTS: A review of the studies shows that vitamin B12, folic acid, and N-acetylcysteine (NAC) have a considerable protective effect on NIHL. However, these protective effects are not yet specified in different frequencies. The findings regarding the protective effects of other antioxidants are inconsistent in this field.

CONCLUSION: Vitamin B12, folic acid, and NAC may have a protective effect as an antioxidant on reducing occupational hearing loss. For a conclusive evidence of vitamin/antioxidant protective therapies, future studies with precise criteria for noise exposure and similar outcome parameters are required.

PMID:33788342 | DOI:10.1002/1348-9585.12217

SOURCE:
Journal of occupational health

PUBLISHER:

PMID:
pubmed:33788342

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33788342

DOI:
10.1002/1348-9585.12217

DATE – PUBLISHED:
Wed, 31 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-31T14:18:59Z

DATE – ADDED:
03/31/21 07:53PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33788342/

LINK – DOI:
https://doi.org/10.1002/1348-9585.12217

LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/1348-9585.12217?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-31T23:53:37+00:00, https://www.hearinglosstreatmentreport.com.

FX-322 in Sensorineural Hearing Loss [Completed]

CATEGORY:
Clinical Trials

TITLE:
FX-322 in Sensorineural Hearing Loss

INTERVENTION/TREATMENT:

PHASE:

DESCRIPTION:
Condition :   Sensorineural Hearing Loss

Interventions :   Drug: FX-322;   Drug: Placebo

Sponsor :   Frequency Therapeutics

Completed

ID:
NCT03616223

STATUS:

DATE – FIRST POSTED:
Mon, 06 Aug 2018 12:00:00 EDT

DATE – LAST UPDATE POSTED:
03/30/21 06:51AM

DATE – RETRIEVED:
03/30/21 06:51AM

LINK – STUDY HISTORY:
https://clinicaltrials.gov/ct2/history/NCT03616223

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT03616223

Transcription Factor Reprogramming in the Inner Ear: Turning on Cell Fate Switches to Regenerate Sensory Hair Cells

https://www.frontiersin.org/articles/10.3389/fncel.2021.660748/full

Front. Cell. Neurosci., 29 March 2021 | https://doi.org/10.3389/fncel.2021.660748
Transcription Factor Reprogramming in the Inner Ear: Turning on Cell Fate Switches to Regenerate Sensory Hair Cells

Abstract

Non-mammalian vertebrates can restore their auditory and vestibular hair cells naturally by triggering the regeneration of adjacent supporting cells. The transcription factor ATOH1 is a key regulator of hair cell development and regeneration in the inner ear. Following the death of hair cells, supporting cells upregulate ATOH1 and give rise to new hair cells. However, in the mature mammalian cochlea, such natural regeneration of hair cells is largely absent. Transcription factor reprogramming has been used in many tissues to convert one cell type into another, with the long-term hope of achieving tissue regeneration. Reprogramming transcription factors work by altering the transcriptomic and epigenetic landscapes in a target cell, resulting in a fate change to the desired cell type. Several studies have shown that ATOH1 is capable of reprogramming cochlear non-sensory tissue into cells resembling hair cells in young animals. However, the reprogramming ability of ATOH1 is lost with age, implying that the potency of individual hair cell-specific transcription factors may be reduced or lost over time by mechanisms that are still not clear. To circumvent this, combinations of key hair cell transcription factors have been used to promote hair cell regeneration in older animals. In this review, we summarize recent findings that have identified and studied these reprogramming factor combinations for hair cell regeneration. Finally, we discuss the important questions that emerge from these findings, particularly the feasibility of therapeutic strategies using reprogramming factors to restore human hearing in the future.

Congenital Deafness and Recent Advances Towards Restoring Hearing Loss

CATEGORY:
Research

SCREENSHOT:
Congenital Deafness and Recent Advances Towards Restoring Hearing Loss

TITLE:
Congenital Deafness and Recent Advances Towards Restoring Hearing Loss

CONTENT:
Curr Protoc. 2021 Mar;1(3):e76. doi: 10.1002/cpz1.76.

ABSTRACT

Congenital hearing loss is the most common birth defect, estimated to affect 2-3 in every 1000 births. Currently there is no cure for hearing loss. Treatment options are limited to hearing aids for mild and moderate cases, and cochlear implants for severe and profound hearing loss. Here we provide a literature overview of the environmental and genetic causes of congenital hearing loss, common animal models and methods used for hearing research, as well as recent advances towards developing therapies to treat congenital deafness. © 2021 The Authors.

PMID:33780161 | DOI:10.1002/cpz1.76

SOURCE:
Current protocols

PUBLISHER:

PMID:
pubmed:33780161

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33780161

DOI:
10.1002/cpz1.76

DATE – PUBLISHED:
Mon, 29 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-29T13:07:03Z

DATE – ADDED:
03/30/21 12:08AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33780161/

LINK – DOI:
https://doi.org/10.1002/cpz1.76

LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/cpz1.76?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-30T04:08:44+00:00, https://www.hearinglosstreatmentreport.com.

HLAA to Hold Patient-Focused Drug Development Webinar for People and Families Living with Sensorineural Hearing Loss (April 8)

HLAA Webinar: Externally-Led Patient-Focused Drug Development Meeting for People and Families Living with Sensorineural Hearing Loss

hlaa-pfdd

This one-hour webinar will provide an overview of the FDA drug development process as well as the value of Patient-Focused Drug Development (PFDD) meetings. We hope this webinar will spike your interest in being part of this important virtual meeting for the hearing loss community taking place on Tuesday, May 25, 2021.

HLAA to Hold Patient-Focused Drug Development Webinar and Meeting

Externally-Led Patient-Focused Drug Development Meeting for People and Families Living with Sensorineural Hearing Loss

Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 – NEK7 mediated inflammasome activation

CATEGORY:
Research

SCREENSHOT:
Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 - NEK7 mediated inflammasome activation

TITLE:
Oridonin ameliorates noise-induced hearing loss by blocking NLRP3 – NEK7 mediated inflammasome activation

CONTENT:
Int Immunopharmacol. 2021 Mar 23;95:107576. doi: 10.1016/j.intimp.2021.107576. Online ahead of print.

ABSTRACT

Inflammation is involved in noise-induced hearing loss (NIHL), but the mechanism is still unknown. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which triggers the inflammatory cascade, has been implicated in several inflammatory diseases in response to oxidative stress. However, whether the NLRP3 inflammasome is a key factor for permanent NIHL is still unknown. In this study, quantitative real-time polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assays (ELISAs) demonstrated that the expression levels of activated caspase-1, interleukin (IL)-1β, IL-18, and NLRP3 were significantly increased in the cochleae of mice exposed to broadband noise (120 dB) for 4 h, compared with the control group. These results indicate that the activation of inflammasomes in the cochleae of mice during the pathological process of NIHL as well as NLRP3, a sensor protein of reactive oxygen species (ROS), may be key factors for inflammasome assembly and subsequent inflammation in cochleae. Moreover, many recent studies have revealed that NEK7 is an important component and regulator of NLRP3 inflammasomes by interacting with NLRP3 directly and that these interactions can be interrupted by oridonin. Here, we further determined that treatment with oridonin could indeed interrupt the interaction between NLRP3 and NEK7 as well as inhibit the downstream inflammasome activation in mouse cochleae after noise exposure. Furthermore, we tested anakinra, another inflammatory inhibitor, and it was shown to partially alleviate the degree of hearing impairment in some frequencies in an NIHL mouse model. These discoveries suggest that inhibiting NLRP3 inflammasomes and the downstream signaling pathway may provide a new strategy for the clinical treatment of NIHL.

PMID:33770730 | DOI:10.1016/j.intimp.2021.107576

SOURCE:
International immunopharmacology

PUBLISHER:

PMID:
pubmed:33770730

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33770730

DOI:
10.1016/j.intimp.2021.107576

DATE – PUBLISHED:
Fri, 26 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-23T12:47:43Z

DATE – ADDED:
03/27/21 10:05AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33770730/

LINK – DOI:
https://doi.org/10.1016/j.intimp.2021.107576

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1567576921002125?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-27T14:05:04+00:00, https://www.hearinglosstreatmentreport.com.

Frequency Therapeutics Releases New Data from Two FX-322 Clinical Studies

https://www.businesswire.com/news/home/20210323005208/en/Frequency-Therapeutics-Releases-New-Data-from-Two-FX-322-Clinical-Studies-Plans-to-Advance-Single-Dose-Regimen

Frequency Therapeutics Releases New Data from Two FX-322 Clinical Studies; Plans to Advance Single-Dose Regimen
Interim FX-322 Phase 2a Results Show Four Injection Schedule Had No Discernible Hearing Benefit

Separate FX-322 Phase 1b Study Confirms Hearing Improvement from Single Injection

Conference call at 8:30am ET today

Prevention of acquired sensorineural hearing loss by in vivo Htra2 gene editing

CATEGORY:
Research

SCREENSHOT:
Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing

TITLE:
Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing

CONTENT:
Genome Biol. 2021 Mar 22;22(1):86. doi: 10.1186/s13059-021-02311-4.

ABSTRACT

BACKGROUND: Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new therapeutic modality for acquired non-inherited sensorineural hearing loss. Here, we develop CRISPR/Cas9 strategies to prevent aminoglycoside-induced deafness, a common type of acquired non-inherited sensorineural hearing loss, via disrupting the Htra2 gene in the inner ear which is involved in apoptosis but has not been investigated in cochlear hair cell protection.

RESULTS: The results indicate that adeno-associated virus (AAV)-mediated delivery of CRISPR/SpCas9 system ameliorates neomycin-induced apoptosis, promotes hair cell survival, and significantly improves hearing function in neomycin-treated mice. The protective effect of the AAV-CRISPR/Cas9 system in vivo is sustained up to 8 weeks after neomycin exposure. For more efficient delivery of the whole CRISPR/Cas9 system, we also explore the AAV-CRISPR/SaCas9 system to prevent neomycin-induced deafness. The in vivo editing efficiency of the SaCas9 system is 1.73% on average. We observed significant improvement in auditory brainstem response thresholds in the injected ears compared with the non-injected ears. At 4 weeks after neomycin exposure, the protective effect of the AAV-CRISPR/SaCas9 system is still obvious, with the improvement in auditory brainstem response threshold up to 50 dB at 8 kHz.

CONCLUSIONS: These findings demonstrate the safe and effective prevention of aminoglycoside-induced deafness via Htra2 gene editing and support further development of the CRISPR/Cas9 technology in the treatment of non-inherited hearing loss as well as other non-inherited diseases.

PMID:33752742 | DOI:10.1186/s13059-021-02311-4

SOURCE:
Genome biology

PUBLISHER:

PMID:
pubmed:33752742

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33752742

DOI:
10.1186/s13059-021-02311-4

DATE – PUBLISHED:
Tue, 23 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-22T09:13:12Z

DATE – ADDED:
03/23/21 07:24AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33752742/

LINK – DOI:
https://doi.org/10.1186/s13059-021-02311-4

LINK – PUBLISHER:
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-021-02311-4?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-23T11:24:13+00:00, https://www.hearinglosstreatmentreport.com.

SCN11A gene deletion causes sensorineural hearing loss by impairing the ribbon synapses and auditory nerves

CATEGORY:
Research

SCREENSHOT:
SCN11A gene deletion causes sensorineural hearing loss by impairing the ribbon synapses and auditory nerves

TITLE:
SCN11A gene deletion causes sensorineural hearing loss by impairing the ribbon synapses and auditory nerves

CONTENT:
BMC Neurosci. 2021 Mar 22;22(1):18. doi: 10.1186/s12868-021-00613-8.

ABSTRACT

BACKGROUND: The SCN11A gene, encoded Nav1.9 TTX resistant sodium channels, is a main effector in peripheral inflammation related pain in nociceptive neurons. The role of SCN11A gene in the auditory system has not been well characterized. We therefore examined the expression of SCN11A in the murine cochlea, the morphological and physiological features of Nav1.9 knockout (KO) ICR mice.

RESULTS: Nav1.9 expression was found in the primary afferent endings beneath the inner hair cells (IHCs). The relative quantitative expression of Nav1.9 mRNA in modiolus of wild-type (WT) mice remains unchanged from P0 to P60. The number of presynaptic CtBP2 puncta in Nav1.9 KO mice was significantly lower than WT. In addition, the number of SGNs in Nav1.9 KO mice was also less than WT in the basal turn, but not in the apical and middle turns. There was no lesion in the somas and stereocilia of hair cells in Nav1.9 KO mice. Furthermore, Nav1.9 KO mice showed higher and progressive elevated ABR threshold at 16 kHz, and a significant increase in CAP thresholds.

CONCLUSIONS: These data suggest a role of Nav1.9 in regulating the function of ribbon synapses and the auditory nerves. The impairment induced by Nav1.9 gene deletion mimics the characters of cochlear synaptopathy.

PMID:33752606 | DOI:10.1186/s12868-021-00613-8

SOURCE:
BMC neuroscience

PUBLISHER:

PMID:
pubmed:33752606

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33752606

DOI:
10.1186/s12868-021-00613-8

DATE – PUBLISHED:
Tue, 23 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-22T13:05:35Z

DATE – ADDED:
03/23/21 08:24AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33752606/

LINK – DOI:
https://doi.org/10.1186/s12868-021-00613-8

LINK – PUBLISHER:
https://bmcneurosci.biomedcentral.com/articles/10.1186/s12868-021-00613-8?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-23T12:24:36+00:00, https://www.hearinglosstreatmentreport.com.

Expression of serum proteins in noise induced hearing loss: insights into potential role in NIHL progression

CATEGORY:
Research

SCREENSHOT:
Expression of serum proteins in noise induced hearing loss workers of mining based industry

TITLE:
Expression of serum proteins in noise induced hearing loss workers of mining based industry

CONTENT:
J Proteomics. 2021 Mar 15:104185. doi: 10.1016/j.jprot.2021.104185. Online ahead of print.

ABSTRACT

Noise Induced Hearing Loss (NIHL) is caused by excessive noise exposure due to occupational activities thus affects communication and quality of life. Prolonged occupational and environmental exposure to loud noise damages key molecules present in the micro-machinery of the ear which are required for the mechano-electrical transduction of sound waves in cochlea. Specific proteins are known to be associated with hearing loss and related structural and functional disabilities in the human inner, outer hair cells and cochlea. Rationale of this study was to identify the cochlear proteins associated with the pathophysiology of NIHL using proteomic approaches in mining based industrial workers. Total (n = 210) samples were collected from mining based industrial workers of central India. Subjects were categorized based on audiometric analysis. Proteome changes of the host serum were investigated using one and two-dimensional electrophoresis in combination with LC-MS/MS and MALDI-TOF MS. Up-regulated 46 cochlear proteins among confirmed NIHL cases were identified by MASCOT. Shrinkage discriminant analysis provided top 25 discriminating feature proteins namely myosin, transthyretin, SERPIN, CCDC50, enkurin, transferin etc. The identified potential proteins may be used as biomarkers for early detection and to understand the pathogenic mechanism of NIHL. Evaluation of these biomarkers in follow-up cases may further aid in improving NIHL diagnosis. SIGNIFICANCE: Human proteome study in Noise Induced Hearing Loss (NIHL) cases has not been published till date. This study represents most comprehensive proteomic analysis in NIHL cases taken from Indian mine workers. The identified key twenty-five discriminating feature proteins which are upregulated when an individual develops (or is in stage of development of) NIHL, provides insights into the potential roles of these varied proteins in disease progression. The proteins thus identified by proteomic approach may be used as early diagnostic biomarker to predict the occurrence of disease at very early stage.

PMID:33737237 | DOI:10.1016/j.jprot.2021.104185

SOURCE:
Journal of proteomics

PUBLISHER:

PMID:
pubmed:33737237

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33737237

DOI:
10.1016/j.jprot.2021.104185

DATE – PUBLISHED:
Fri, 19 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-18T20:32:33Z

DATE – ADDED:
03/19/21 03:00PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33737237/

LINK – DOI:
https://doi.org/10.1016/j.jprot.2021.104185

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S1874391921000841?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-19T19:00:02+00:00, https://www.hearinglosstreatmentreport.com.

The DNA methylation inhibitor RG108 protects against noise-induced hearing loss

CATEGORY:
Research

SCREENSHOT:
The DNA methylation inhibitor RG108 protects against noise-induced hearing loss

TITLE:
The DNA methylation inhibitor RG108 protects against noise-induced hearing loss

CONTENT:
Cell Biol Toxicol. 2021 Mar 15. doi: 10.1007/s10565-021-09596-y. Online ahead of print.

ABSTRACT

BACKGROUND: Noise-induced hearing loss represents a commonly diagnosed type of hearing disability, severely impacting the quality of life of individuals. The current work is aimed at assessing the effects of DNA methylation on noise-induced hearing loss.

METHODS: Blocking DNA methyltransferase 1 (DNMT1) activity with a selective inhibitor RG108 or silencing DNMT1 with siRNA was used in this study. Auditory brainstem responses were measured at baseline and 2 days after trauma in mice to assess auditory functions. Whole-mount immunofluorescent staining and confocal microcopy of mouse inner ear specimens were performed to analyze noise-induced damage in cochleae and the auditory nerve at 2 days after noise exposure.

RESULTS: The results showed that noise exposure caused threshold elevation of auditory brainstem responses and cochlear hair cell loss. Whole-mount cochlea staining revealed a reduction in the density of auditory ribbon synapses between inner hair cells and spiral ganglion neurons. Inhibition of DNA methyltransferase activity via a non-nucleoside specific pharmacological inhibitor, RG108, or silencing of DNA methyltransferase-1 with siRNA significantly attenuated ABR threshold elevation, hair cell damage, and the loss of auditory synapses.

CONCLUSIONS: This study suggests that inhibition of DNMT1 ameliorates noise-induced hearing loss and indicates that DNMT1 may be a promising therapeutic target. Graphical Headlights • RG108 protected against noise-induced hearing loss • RG108 administration protected against noise-induced hair cell loss and auditory neural damage. • RG108 administration attenuated oxidative stress-induced DNA damage and subsequent apoptosis-mediated cell loss in the cochlea after noise exposure.

PMID:33723744 | DOI:10.1007/s10565-021-09596-y

SOURCE:
Cell biology and toxicology

PUBLISHER:

PMID:
pubmed:33723744

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33723744

DOI:
10.1007/s10565-021-09596-y

DATE – PUBLISHED:
Tue, 16 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-15T18:03:14Z

DATE – ADDED:
03/16/21 02:49PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33723744/

LINK – DOI:
https://doi.org/10.1007/s10565-021-09596-y

LINK – PUBLISHER:
http://link.springer.com/10.1007/s10565-021-09596-y?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-16T18:49:43+00:00, https://www.hearinglosstreatmentreport.com.

Hidden hearing loss is associated with loss of ribbon synapses of cochlea inner hair cells

CATEGORY:6
Research

SCREENSHOT:
Hidden hearing loss is associated with loss of ribbon synapses of cochlea inner hair cells

TITLE:
Hidden hearing loss is associated with loss of ribbon synapses of cochlea inner hair cells

CONTENT:
Biosci Rep. 2021 Mar 18:BSR20201637. doi: 10.1042/BSR20201637. Online ahead of print.

ABSTRACT

This study aimed to observe the changes in the cochlea ribbon synapses after repeated exposure to moderate-to-high intensity noise. Guinea pigs received 95 dB SPL white noise exposure 4 hours a day for consecutive 7 days (we regarded it a medium-term and moderate-intensity noise, or MTMI noise). Animals were divided into 4 groups: Control, 1DPN (1-day post noise), 1WPN (1-week post noise), and 1MPN (1-month post noise). Auditory function analysis by ABR and CAP recordings, as well as ribbon synapse morphological analyses by immunohistochemistry (Ctbp2 and PSD95 staining) were performed one day, one week, and one month after noise exposure. After MTMI noise exposure, the amplitudes of auditory brainstem response (ABR) I and III waves were suppressed. The compound action potential (CAP) threshold was elevated, and CAP amplitude was reduced in the 1DPN group. No apparent changes in hair cell shape, arrangement or number were observed, but the number of ribbon synapse was reduced. The 1WPN and 1MPN groups showed that part of ABR and CAP changes recovered, as well as the synapse number. The defects in cochlea auditory function and synapse changes were observed mainly in the high-frequency region. Together, repeated exposure in MTMI noise can cause hidden hearing loss, which is partially reversible after leaving the noise environment; and MTMI noise induced hidden hearing loss is associated with inner hair cell ribbon synapses.

PMID:33734328 | DOI:10.1042/BSR20201637

SOURCE:
Bioscience reports

PUBLISHER:

PMID:
pubmed:33734328

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33734328

DOI:
10.1042/BSR20201637

DATE – PUBLISHED:
Thu, 18 Mar 2021 06:00:00 -0400

DATE – DOI:
2021-03-18T15:54:01Z

DATE – ADDED:
03/18/21 07:41PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33734328/

LINK – DOI:
https://doi.org/10.1042/BSR20201637

LINK – PUBLISHER:
https://portlandpress.com/bioscirep/article/doi/10.1042/BSR20201637/228102/Hidden-hearing-loss-is-associated-with-loss-of?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-18T23:41:43+00:00, https://www.hearinglosstreatmentreport.com.

VEGF-A165 restores vascular function to the inner ear and could potentially reverse common forms of hearing loss…

Could improving poor blood supply to the damaged inner ear reverse noise-induced and/or age-related hearing loss?

Yes, according to some fascinating new research from Zhang et al, published yesterday on March 9, 2021, that describes a unique approach to hearing restoration that is backed by “clear-cut evidence”…

VEGF-A165 article screenshot
This VEGF-A165 research paper is hot off the press!!!

Here is a link to a full-text PDF copy of the paper (and all the science-y details):

VEGF-A165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss [PDF]

Sneak preview of the abstract:

When hearing loss is caused by noise or aging, it is often associated with breakdown of the barrier between the cochlea and its blood vessels. Pericytes populate many small vessels in the adult inner ear, however, their role in different forms of hearing loss is largely unknown. Using an inducible and conditional pericyte depletion mouse model, we show that loss of pericytes leads to marked changes in vascular structure, resulting in poor blood circulation and hearing loss. In vitro, using advanced tissue explants from pericyte fluorescence reporter models in combination with exogenous donor pericytes, we show pericytes, signaled by endothelial growth factor isoform A165 (VEGF-A165), vigorously drives new vessel growth in both adult and neonatal mouse inner ear tissue. In vivo, the delivery of an adeno-associated virus serotype 1 (AAV1)-mediated VEGF-A165 viral vector to pericyte depleted animals regenerated lost pericytes, improved blood supply, reduced loss of sensory hair cells, and attenuated hearing loss. These studies provide the first clear-cut evidence that pericytes are critical for adult hearing and can regenerate cochlear vasculature. The restoration of vascular function in the damaged inner ear with AAV1-mediated VEGF-A165 gene therapy is a new strategy for ameliorating vascular associated hearing disorders, including common forms of age-related hearing loss.

SOURCE: Zhang et al. Published March 9, 2021. JCI Insight 2021. https://doi.org/10.1172/jci.insight.143285.

That’s all for now.

The Hearing Loss Treatment Report system will be monitoring the scientific literature and news for any further mentions of VEGF-A165… including any progress it makes toward that first big milestone: human clinical trials.

We don’t have a timeline for you (yet)… but you can expect some follow-up coverage in the coming weeks/months.

Stay tuned.

RE: how to get VEGF-A165 updates

To follow what’s happening with VEGF-A165 (as well as other treatments such as FX-322, OTO-413, PIPE-505), I encourage you to sign up for Hearing Loss Treatment Report email updates. These updates are 100% free… your information is kept private, and… you won’t get any spammy marketing emails or promotional emails. That’s a promise. Instead, you will only receive important (and often exclusive) updates related to up-and-coming hearing loss treatments and scientific breakthroughs.

Questions? Comments? Feedback?

Send an email to michael@urgentresearch.com and speak your mind.

I read every email and try my best to reply (thoughtfully) within 1-2 days.

P.S. Do you like these “exclusive” update posts?
Kindly share them with people you know who might find them interesting.

Advances and challenges in adeno-associated viral inner-ear gene therapy for sensorineural hearing loss

CATEGORY:
Research

SCREENSHOT:
Advances and challenges in adeno-associated viral inner-ear gene therapy for sensorineural hearing loss

TITLE:
Advances and challenges in adeno-associated viral inner-ear gene therapy for sensorineural hearing loss

CONTENT:
Mol Ther Methods Clin Dev. 2021 Mar 10;21:209-236. doi: 10.1016/j.omtm.2021.03.005. eCollection 2021 Jun 11.

ABSTRACT

There is growing attention and effort focused on treating the root cause of sensorineural hearing loss rather than managing associated secondary characteristic features. With recent substantial advances in understanding sensorineural hearing-loss mechanisms, gene delivery has emerged as a promising strategy for the biological treatment of hearing loss associated with genetic dysfunction. There are several successful and promising proof-of-principle examples of transgene deliveries in animal models; however, there remains substantial further progress to be made in these avenues before realizing their clinical application in humans. Herein, we review different aspects of development, ongoing preclinical studies, and challenges to the clinical transition of transgene delivery of the inner ear toward the restoration of lost auditory and vestibular function.

PMID:33850952 | PMC:PMC8010215 | DOI:10.1016/j.omtm.2021.03.005

SOURCE:
Molecular therapy. Methods & clinical development

PUBLISHER:

PMID:
pubmed:33850952

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33850952

DOI:
10.1016/j.omtm.2021.03.005

DATE – PUBLISHED:
Wed, 14 Apr 2021 06:00:00 -0400

DATE – DOI:
2021-03-11T08:48:48Z

DATE – ADDED:
04/14/21 04:52PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33850952/

LINK – DOI:
https://doi.org/10.1016/j.omtm.2021.03.005

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S2329050121000450?utm_source=hearinglosstreatmentreport.com

https://www.cell.com/molecular-therapy-family/methods/fulltext/S2329-0501(21)00045-0

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-04-14T20:52:40+00:00, https://www.hearinglosstreatmentreport.com.

High Dose Oral Steroids in Sudden Sensorineural Hearing Loss

CATEGORY:
Clinical Trials

TITLE:
High Dose Oral Steroids in Sudden Sensorineural Hearing Loss

INTERVENTION/TREATMENT:

PHASE:

DESCRIPTION:
Condition :   Sudden Sensorineural Hearing Loss (SSNHL)

Interventions :   Drug: Dexamethasone;   Drug: Prednisone

Sponsor :   University of Colorado, Denver

Recruiting

ID:
NCT03255473

STATUS:

DATE – FIRST POSTED:
Mon, 21 Aug 2017 12:00:00 EDT

DATE – LAST UPDATE POSTED:
03/10/21 06:35AM

DATE – RETRIEVED:
03/10/21 06:35AM

LINK – STUDY HISTORY:
https://clinicaltrials.gov/ct2/history/NCT03255473

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT03255473

VEGF-A165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss

CATEGORY:
Research

SCREENSHOT:
VEGF-A165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss

TITLE:
VEGF-A165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss

CONTENT:
JCI Insight. 2021 Mar 9:143285. doi: 10.1172/jci.insight.143285. Online ahead of print.

ABSTRACT

AbstractMillions of people are affected by hearing loss. When hearing loss is caused by noise or aging, it is often associated with breakdown of the barrier between the cochlea and its blood vessels. Pericytes populate many small vessels in the adult inner ear, however, their role in different forms of hearing loss is largely unknown. Using an inducible and conditional pericyte depletion mouse model, we show that loss of pericytes leads to marked changes in vascular structure, resulting in poor blood circulation and hearing loss. In vitro, using advanced tissue explants from pericyte fluorescence reporter models in combination with exogenous donor pericytes, we show pericytes, signaled by endothelial growth factor isoform A165 (VEGF-A165), vigorously drives new vessel growth in both adult and neonatal mouse inner ear tissue. In vivo, the delivery of an adeno-associated virus serotype 1 (AAV1)-mediated VEGF-A165 viral vector to pericyte depleted animals regenerated lost pericytes, improved blood supply, reduced loss of sensory hair cells, and attenuated hearing loss. These studies provide the first clear-cut evidence that pericytes are critical for adult hearing and can regenerate cochlear vasculature. The restoration of vascular function in the damaged inner ear with AAV1-mediated VEGF-A165 gene therapy is a new strategy for ameliorating vascular associated hearing disorders, including common forms of age-related hearing loss.

PMID:33690221 | DOI:10.1172/jci.insight.143285

SOURCE:
JCI insight

PUBLISHER:

PMID:
pubmed:33690221

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33690221

DOI:
10.1172/jci.insight.143285

DATE – PUBLISHED:
Wed, 10 Mar 2021 06:00:00 -0500

DATE – DOI:
2021-03-09T17:03:21Z

DATE – ADDED:
03/10/21 10:18PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33690221/

LINK – DOI:
https://doi.org/10.1172/jci.insight.143285

LINK – PUBLISHER:
http://insight.jci.org/articles/view/143285?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-11T03:18:27+00:00, https://www.hearinglosstreatmentreport.com.

Treatment of Long-term Sudden Sensorineural Hearing Loss as an Otologic Migraine Phenomenon

CATEGORY:
Research

SCREENSHOT:
Treatment of Long-term Sudden Sensorineural Hearing Loss as an Otologic Migraine Phenomenon

TITLE:
Treatment of Long-term Sudden Sensorineural Hearing Loss as an Otologic Migraine Phenomenon

CONTENT:
Otol Neurotol. 2021 Mar 5. doi: 10.1097/MAO.0000000000003111. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe a cohort of patients presenting with long-term sudden sensorineural hearing loss (SSNHL) treated with prophylactic migraine and intratympanic steroid therapy.

METHODS: Patients presenting to a neurotology clinic at least 6 weeks from SSNHL onset were included. All patients received migraine prophylactic medication (nortriptyline, topiramate, and/or verapamil) and lifestyle changes for at least 6 weeks, as well as intratympanic steroid injections, if appropriate.

RESULTS: Twenty-one patients (43% female) with a mean age of 64 ± 11 years who presented 9 ± 8 months (median = 5) from symptom onset were included. Posttreatment hearing thresholds were significantly improved compared with pretreatment thresholds at 500 Hz (49 ± 19 dB versus 55 ± 20 dB, p = 0.01), 1000 Hz (52 ± 19 dB versus 57 ± 21 dB, p = 0.03), low-frequency pure-tone average (53 ± 15 dB versus 57 ± 17 dB, p = 0.01), and speech-frequency pure-tone average (57 ± 13 dB versus 60 ± 15 dB, p = 0.02). Posttreatment word-recognition-score (WRS) and speech-recognition-threshold (SRT) were also significantly improved (45 ± 28% versus 70 ± 28% and 57 ± 18 dB versus 50 ± 16 dB, respectively, both p < 0.01). Notably, ≥15% improvement in WRS and ≥10 dB improvement in SRT was observed in 13 (68%) and 8 (40%) patients, respectively. Of the 11 patients who presented with initial < 50% WRS, 8 (73%) had improved posttreatment >50% WRS with an average improvement of 39 ± 9%.

CONCLUSIONS: Migraine medications in addition to intratympanic steroid injections significantly improved SRT and hearing frequencies in 40% and 29% of SSNHL patients, respectively, while significant WRS recovery was observed in most (68%) patients. This suggests SSNHL may be an otologic migraine phenomenon, which may be at least partially reversible even after the traditional 30-day postonset window.

PMID:33710150 | DOI:10.1097/MAO.0000000000003111

SOURCE:
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology

PUBLISHER:

PMID:
pubmed:33710150

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33710150

DOI:
10.1097/MAO.0000000000003111

DATE – PUBLISHED:
Fri, 12 Mar 2021 06:00:00 -0500

DATE – DOI:
2021-03-12T14:03:36Z

DATE – ADDED:
03/12/21 01:58PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33710150/

LINK – DOI:
https://doi.org/10.1097/MAO.0000000000003111

LINK – PUBLISHER:
https://journals.lww.com/10.1097/MAO.0000000000003111?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-03-12T18:58:06+00:00, https://www.hearinglosstreatmentreport.com.

Research center at Creighton University awarded $10.8 million NIH grant to help researchers discover new drugs for hearing loss

https://www.newswise.com/articles/translational-hearing-center-awarded-largest-nih-grant-in-creighton-university-history

Translational Hearing Center awarded largest NIH grant in Creighton University history
NIH grant to help researchers translate basic hearing loss research into practical therapies

Research center at Creighton University awarded $10.8 million NIH grant to help researchers discover new drugs for hearing loss

Phase I/IIa Study Evaluating Safety and Efficacy of an Intratympanic Dose of PIPE-505 in Subjects With Hearing Loss

CATEGORY:
Clinical Trials

TITLE:
Phase I/IIa Study Evaluating Safety and Efficacy of an Intratympanic Dose of PIPE-505 in Subjects With Hearing Loss

INTERVENTION/TREATMENT:

PHASE:

DESCRIPTION:
Condition :   Sensorineural Hearing Loss

Interventions :   Drug: PIPE-505;   Drug: Diluent alone

Sponsor :   Pipeline Therapeutics, Inc.

Recruiting

ID:
NCT04462198

STATUS:

DATE – FIRST POSTED:
Wed, 08 Jul 2020 12:00:00 EDT

DATE – LAST UPDATE POSTED:
10/14/20 08:47PM

DATE – RETRIEVED:
10/14/20 08:47PM

LINK – STUDY HISTORY:
https://clinicaltrials.gov/ct2/history/NCT04462198

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT04462198

Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss

CATEGORY:
Research

SCREENSHOT:
Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss

TITLE:
Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss

CONTENT:
Int J Mol Sci. 2021 Mar 2;22(5):2510. doi: 10.3390/ijms22052510.

ABSTRACT

Potassium voltage-gated channel subfamily q member 4 (KCNQ4) is a voltage-gated potassium channel that plays essential roles in maintaining ion homeostasis and regulating hair cell membrane potential. Reduction of the activity of the KCNQ4 channel owing to genetic mutations is responsible for nonsyndromic hearing loss, a typically late-onset, initially high-frequency loss progressing over time. In addition, variants of KCNQ4 have also been associated with noise-induced hearing loss and age-related hearing loss. Therefore, the discovery of small compounds activating or potentiating KCNQ4 is an important strategy for the curative treatment of hearing loss. In this review, we updated the current concept of the physiological role of KCNQ4 in the inner ear and the pathologic mechanism underlying the role of KCNQ4 variants with regard to hearing loss. Finally, we focused on currently developed KCNQ4 activators and their pros and cons, paving the way for the future development of specific KCNQ4 activators as a remedy for hearing loss.

PMID:33801540 | DOI:10.3390/ijms22052510

SOURCE:
International journal of molecular sciences

PUBLISHER:

PMID:
pubmed:33801540

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33801540

DOI:
10.3390/ijms22052510

DATE – PUBLISHED:
Sat, 03 Apr 2021 06:00:00 -0400

DATE – DOI:
2021-03-03T02:30:13Z

DATE – ADDED:
04/03/21 05:12PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33801540/

LINK – DOI:
https://doi.org/10.3390/ijms22052510

LINK – PUBLISHER:
https://www.mdpi.com/1422-0067/22/5/2510/htm
https://www.mdpi.com/1422-0067/22/5/2510?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-04-03T21:12:02+00:00, https://www.hearinglosstreatmentreport.com.

Verification of the Efficacy/Safety of the Dual Drug Delivery for Hearing Loss

https://clinicaltrials.gov/ct2/show/NCT04766853

Verification of the Efficacy/Safety of the Dual Drug Delivery for Hearing Loss

Brief Summary:
This study is a prospective, randomized pilot study. To verify an efficacy and safety of the dual drug injectable delivery vehicle, patients who have not responded to the existing standard treatment will be enrolled. Hearing test and endoscopy of tympanic membrane will be conducted after intratympanic treatment for evaluation.

Condition or disease Intervention/treatment Phase
Hearing Loss, Sudden
Hearing Loss Ototoxic
Hearing Loss, Noise-Induced
Meniere Disease
Drug: Dexamethasone
Drug: Hyaluronic acid
Phase 1
Phase 2

Study Design
Go to sections
Study Type : Interventional (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Verification of the Efficacy / Safety of the Dual Drug Injectable Delivery Vehicle for Treating Intractable Hearing Loss (Pilot Study)
Estimated Study Start Date : March 2021
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : February 2022

Promise of Optogenetics ‘Sheds Light’ on Hearing Restoration

https://journals.lww.com/thehearingjournal/Fulltext/2021/03000/Promise_of_Optogenetics__Sheds_Light__on_Hearing.1.aspx

Promise of Optogenetics ‘Sheds Light’ on Hearing Restoration
Glantz, Gordon

The Hearing Journal: March 2021 – Volume 74 – Issue 3 – p 20,22,23
doi: 10.1097/01.HJ.0000737552.03771.a4

Frequency Therapeutics Announces Publication of FX-322 Phase 1/2 Data Showing Hearing Improvements in Sensorineural Hearing Loss Patients

https://www.businesswire.com/news/home/20210222005818/en/Frequency-Therapeutics-Announces-Publication-of-Phase-12-Data-Showing-Hearing-Improvements-in-Acquired-Sensorineural-Hearing-Loss-Patients-Receiving-FX-322

Frequency Therapeutics Announces Publication of Phase 1/2 Data Showing Hearing Improvements in Acquired Sensorineural Hearing Loss Patients Receiving FX-322
Results Published in Leading Peer-Reviewed Otolaryngology Journal, Otology & Neurotology

Statistically Significant Improvements Observed in Word Recognition Tests in Quiet and in Noise; Suggests Potential to Improve Speech Intelligibility, a Major Unmet Need for Individuals with Hearing Loss

Company Expects Interim FX-322 Phase 2a Study Data Later this Quarter

https://journals.lww.com/otology-neurotology/Abstract/9000/Improved_Speech_Intelligibility_in_Subjects_With.95768.aspx

T2 relaxation time shortening in the cochlea of patients with sudden sensory neuronal hearing loss: changes in inner ear fluid composition implicated in idiopathic SSNHL development

CATEGORY:
Research

SCREENSHOT:
T2 relaxation time shortening in the cochlea of patients with sudden sensory neuronal hearing loss: a retrospective study using quantitative synthetic magnetic resonance imaging Screenshot

TITLE:
T2 relaxation time shortening in the cochlea of patients with sudden sensory neuronal hearing loss: a retrospective study using quantitative synthetic magnetic resonance imaging

CONTENT:
Eur Radiol. 2021 Feb 20. doi: 10.1007/s00330-021-07749-5. Online ahead of print.

ABSTRACT

OBJECTIVES: High cochlear signal intensity on three-dimensional (3D) T2 fluid-attenuated inversion recovery (FLAIR) sequences in patients with sudden sensorineural hearing loss (SSNHL) has been reported. Here, we evaluated the cochlear T2 relaxation time differences in patients with idiopathic SSNHL using quantitative synthetic MRI (SyMRI).

METHODS: Twenty-four patients with unilateral SSNHL who underwent precontrast conventional 3D FLAIR and SyMRI were retrospectively included. T1 and T2 relaxation times and the proton density (PD) of the bilateral ears were measured by manually drawn regions of interest. Wilcoxon signed-rank tests and intra- and interobserver correlation analyses were performed. Qualitative analysis was also performed to determine the presence and laterality of the asymmetric high signal intensity on synthetic FLAIR (SyFLAIR) images.

RESULTS: The T2 relaxation time was significantly lower in the affected (basal and apico-middle turns) than in the unaffected cochlea (basal turn: 519 ± 181.3 vs. 608.8 ± 203.6, p = 0.042; apico-middle turn: 410.8 ± 163.8 vs. 514.5 ± 186.3, p = 0.037). There were no significant differences in the T1 relaxation time and PD between the affected and unaffected ears (p > 0.05). Additionally, three patients without asymmetric signal intensity on conventional MRI showed asymmetric increased signal intensity in the affected ear on SyFLAIR.

CONCLUSIONS: The T2 relaxation time was significantly shorter in the affected than in the unaffected cochlea of patients with idiopathic SSNHL. The SyMRI-derived T2 relaxation time may be a promising imaging marker, suggesting that the changes in inner ear fluid composition are implicated in the idiopathic SSNHL development.

KEY POINTS: • T2 relaxation time was significantly lower in the affected than in the unaffected cochlea. • SyFLAIR showed increased lesion conspicuity compared to conventional 3D-FLAIR in detecting asymmetric high signal intensity of the affected side. • SyMRI-derived T2 relaxation time may be a promising imaging marker of the affected ear in patients with idiopathic SSNHL.

PMID:33609144 | DOI:10.1007/s00330-021-07749-5

SOURCE:
European radiology

PUBLISHER:

PMID:
pubmed:33609144

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33609144

DOI:
10.1007/s00330-021-07749-5

DATE – PUBLISHED:
Sat, 20 Feb 2021 06:00:00 -0500

DATE – DOI:
2021-02-20T17:19:51Z

DATE – ADDED:
02/21/21 01:27AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33609144/

LINK – DOI:
https://doi.org/10.1007/s00330-021-07749-5

LINK – PUBLISHER:
http://link.springer.com/10.1007/s00330-021-07749-5

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-02-21T06:27:26+00:00, https://www.hearinglosstreatmentreport.com.

Sensorion Presents New Preclinical Data on SENS-401 at ARO 2021: significant treatment benefits in rats with severe hearing loss when initiated within 7 days of acoustic trauma

https://www.businesswire.com/news/home/20210218006082/en/Sensorion-Presents-New-Preclinical-Data-on-SENS-401-at-ARO-2021

Sensorion Presents New Preclinical Data on SENS-401 at ARO 2021
SENS-401 yields significant treatment benefits in rats with severe hearing loss when initiated with a delay up to 7 days after the initial acoustic trauma
Sensorion presenting three posters at Association for Research in Otolaryngology (ARO) meeting
ARO will be hosted virtually on February 20-24, 2021

Reduction of α2-Na/K-ATPase might play an important role in the pathogenesis of age-related hearing loss

CATEGORY:
Research

SCREENSHOT:
Expression of alpha2-Na/K-ATPase in C57BL/6J Mice Inner Ear and Its Relationship with Age-related Hearing Loss Screenshot

TITLE:
Expression of alpha2-Na/K-ATPase in C57BL/6J Mice Inner Ear and Its Relationship with Age-related Hearing Loss

CONTENT:
Curr Med Sci. 2021 Feb;41(1):153-157. doi: 10.1007/s11596-021-2330-5. Epub 2021 Feb 13.

ABSTRACT

K+ cycling in the cochlea is critical to maintain hearing. Many sodium-potassium pumps are proved to participate in K+ cycling, such as Na/K-ATPase. The α2-Na/K-ATPase is an important isoform of Na/K-ATPase. The expression of α2-Na/K-ATPase in the cochlea is not clear. In this study, we used C57BL/6 mice as a model of presbycusis and implemented immunohistochemistry staining and quantitative real time-PCR, and the α2-Na/K-ATPase expression pattern was confirmed in the inner ear. It was found α2-Na/K-ATPase was expressed widely in cochlea and its mRNA and protein expression was gradually reduced with aging (4-, 14-, 26- and 48-weeks old mice). We suspected that, the down-regulation of α2-Na/K-ATPase expression might be associated with the remodeling of K+ cycling, degeneration of morphological structure and decrease of hearing function in aging C57 mice. In conclusion, we speculated that the reduction of α2-Na/K-ATPase might play an important role in the pathogenesis of age-related hearing loss.

PMID:33582920 | DOI:10.1007/s11596-021-2330-5

SOURCE:
Current medical science

PUBLISHER:

PMID:
pubmed:33582920

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33582920

DOI:
10.1007/s11596-021-2330-5

DATE – PUBLISHED:
Sun, 14 Feb 2021 06:00:00 -0500

DATE – DOI:
2021-02-14T09:43:18Z

DATE – ADDED:
02/15/21 01:12AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33582920/

LINK – DOI:
https://doi.org/10.1007/s11596-021-2330-5

LINK – PUBLISHER:
http://link.springer.com/10.1007/s11596-021-2330-5

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-02-15T06:12:41+00:00, https://www.hearinglosstreatmentreport.com.

OTO-413 Phase 1/2 trial expansion in hearing loss expected to start in Q2 2021 with results anticipated in mid-2022

https://www.globenewswire.com/news-release/2021/02/11/2174562/0/en/Otonomy-Reports-Fourth-Quarter-and-Full-Year-2020-Financial-Results-and-Provides-Corporate-Update.html

Otonomy Reports Fourth Quarter and Full Year 2020 Financial Results and Provides Corporate Update

February 11, 2021 16:17 ET | Source: Otonomy, Inc.
OTIVIDEX® Phase 3 trial results in Ménière’s disease expected by end of February
OTO-313 Phase 2 trial in tinnitus planned to start in first quarter of 2021 with top-line results expected in mid-2022
OTO-413 Phase 1/2 trial expansion in hearing loss expected to start in second quarter of 2021 with results anticipated in mid-2022

Frequency Therapeutics Appoints Kevin Franck, Ph.D., as Senior Vice President, Strategic Marketing and New Product Planning… to help lead pre-commercial strategy and launch planning for FX-322 (and its potential commercialization both in the US and internationally)…

https://www.businesswire.com/news/home/20210208005168/en/Frequency-Therapeutics-Appoints-Kevin-Franck-Ph.D.-as-Senior-Vice-President-Strategic-Marketing-and-New-Product-Planning

Frequency Therapeutics Appoints Kevin Franck, Ph.D., as Senior Vice President, Strategic Marketing and New Product Planning… to help lead pre-commercial strategy and launch planning for FX-322 and for potential commercialization in the US…

Frequency Therapeutics Appoints Kevin Franck, Ph.D., as Senior Vice President, Strategic Marketing and New Product Planning
Dr. Franck joins from Massachusetts Eye and Ear, where he was Director of Audiology and Harvard Medical School Faculty in the Department of Otolaryngology-Head and Neck Surgery

February 08, 2021 07:00 AM Eastern Standard Time
WOBURN, Mass.–(BUSINESS WIRE)–Frequency Therapeutics, Inc. (Nasdaq: FREQ), a clinical-stage biotechnology company focused on harnessing the body’s innate biology to repair or reverse damage caused by a broad range of degenerative diseases, today announced the appointment of Kevin Franck, Ph.D., as Senior Vice President of Strategic Marketing and New Product Planning. Dr. Franck will lead pre-commercial strategy and launch planning for Frequency’s clinical pipeline, including its lead program aimed at developing a restorative treatment for sensorineural hearing loss (SNHL), the most common form of hearing loss.

New pill [SPI-1005] that may help improve age-related hearing loss by protecting delicate hair cells in the inner ear

https://www.dailymail.co.uk/health/article-9238361/New-pill-help-hear-clearly-protecting-delicate-hair-cells-inner-ear.html

New pill that may help improve age-related hearing loss by protecting delicate hair cells in the inner ear
A new drug, SPI-1005, aids hearing by protecting delicate hair cells in inner ear
It is also being tested in U.S. as a potential treatment for patients with Covid-19
The number of auditory hair cells declines due to age, disease and loud noise

PREVIEW: “Preclinical/Clinical Translational Evidence for a Potential Hearing Restoration Therapeutic, FX-322” [ARO 2021 Podium Presentation]

Here is a sneak preview of an upcoming podium presentation from Will McLean (Frequency Therapeutics) about hearing restoration and FX-322:

FX-322 podium abstract for ARO February 2021

What’s happening:

In less than two weeks from today, the 44th Annual ARO MidWinter Meeting will begin.

It is a virtual conference.

On Monday, February 22, 2021, Will McLean (Frequency Therapeutics) will give a podium presentation at this virtual conference.

Topic? FX-322…

Here is a copy of McLean’s podium abstract:

Preclinical/Clinical Translational Evidence for a Potential Hearing Restoration Therapeutic, FX-322

Background: Cochlear hair cell loss in mammals is permanent because progenitor cells fail to divide and differentiate on their own. Previous work has shown that the two compounds in FX-322 enhance the regenerative potential of mouse and human progenitor cells in vitro. This multi-group collaboration assessed the pharmacodynamic (PD) and restorative potential of FX-322 in a mouse noise-induced hearing loss (NIHL) model, cochlear pharmacokinetics (PK) of intratympanically injected FX-322 in guinea pigs, perilymph concentrations in patients undergoing cochlear implantation, and a safety study of FX-322 in patients with permanent sensorineural hearing loss (SNHL).

Methods: PD effects were first assessed in a NIHL mouse model to assess the therapeutic potential of FX-322. PK studies with FX-322 were performed in guinea pigs to calibrate a well-established computer model predicting drug distribution over the length of the cochlea with time. The animal PK model was extended to humans by analysis of perilymph samples collected from subjects undergoing cochlear implant surgery. A double-blinded, placebo-controlled, safety trial in patients with permanent/stable SNHL was conducted to assess the systemic safety, plasma PK, and effects on otoscopy, audiometry, and word testing (WR, WIN). The trial enrolled 23 patients with medical histories consistent with either NIHL or sudden SNHL. Treatment was a single unilateral intratympanic dose and patients were monitored overnight for safety, PK and PD over a 90-day period.

Results: Animal PD – A single intratympanic injection of FX322 was associated with increased hair cell counts and improved auditory function compared to placebo in mice with NIHL within one month after treatment. Guinea Pig PK – FX-322 concentrations in samples taken from the RW niche were found to decrease with time, with elimination half-times under 1 hour. The highest drug concentration was observed in the basal regions. Human PK – Intraoperative middle ear contents and perilymph were analyzed for FX-322 approximately 1 hour into surgery for cochlear implant subjects (n=7). While some subjects had anatomical features that have been speculated to impair drug entry, such as mucosal folds or bony overhangs, FX-322 was quantified in all samples analyzed. Human Safety and PD – FX-322 was associated with a favorable safety profile. In FX-322-treated subject ears WR and WIN improved over the duration of the study while placebo-treated subject ears did not.

Conclusions: Both preclinical and clinical PK analyses suggest that FX-322 was able to achieve therapeutically active levels in the extended high frequency region of the cochlea. Preclinically, this was associated with an increase in hair cell counts and auditory brainstem response thresholds. The present work provides the first evidence that a novel potential therapeutic, FX-322, is associated with clinically meaningful improvements in speech recognition in subjects with permanent and stable SNHL, and larger clinical studies are underway.

The source of this “podium abstract” is the Association for Research in Otolaryngology (ARO)’s 44th Annual Mid-Winter Meeting event website.

Here is a link to the official PDF copy of the February 22, 2021 FX-322 podium presentation [EDIT #1: the link does not work, removed] (uploaded online by ARO’s event organizers… who have once again done a superb job organizing all of the presentations, speakers, podiums, posters, and more, into a friendly and searchable format *even when some links don’t work!).

What’s “new” here?

For readers who have been closely following FX-322 updates… there is nothing truly “new” in this presentation preview. However, we do not know what other data or information or announcements will be shared alongside this presentation. Perhaps we will also get a press release on Monday, February 22 which gives us more substantial “news” *fingers crossed*…

RE: FX-322 updates…

If you’re interested in news updates RE: the very latest hearing loss treatments and recent progress toward potential cures… remember to sign up for the HearingLossTreatmentReport.com email newsletter. It’s 100% free and the goal is to give you an easy (and fast) way to get updates about FX-322 and other promising hearing restoration therapeutics – earlier… often days (and sometimes weeks) ahead of “mainstream” sources.

Questions? Comments? Feedback? Send an email to michael@urgentresearch.com and say hello.

An antibody to RGMa promotes regeneration of cochlear synapses after noise exposure

https://www.nature.com/articles/s41598-021-81294-5

An antibody to RGMa promotes regeneration of cochlear synapses after noise exposure

Treatment of noise-exposed animals with an anti-RGMa blocking antibody regenerated inner hair cell synapses and resulted in recovery of wave-I amplitude of the auditory brainstem response, indicating effective reversal of synaptopathy.

COMMENT: see preprint from July 2, 2020
https://www.biorxiv.org/content/10.1101/2020.07.01.183269v1.full

Stem Cells and Gene Therapy in Progressive Hearing Loss: the State of the Art

CATEGORY:
Research

SCREENSHOT:
Stem Cells and Gene Therapy in Progressive Hearing Loss: the State of the Art Screenshot

TITLE:
Stem Cells and Gene Therapy in Progressive Hearing Loss: the State of the Art

CONTENT:
J Assoc Res Otolaryngol. 2021 Jan 28. doi: 10.1007/s10162-020-00781-0. Online ahead of print.

ABSTRACT

Progressive non-syndromic sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment, affecting more than a third of individuals over the age of 65. PNSHL includes noise-induced hearing loss (NIHL) and inherited forms of deafness, among which is delayed-onset autosomal dominant hearing loss (AD PNSHL). PNSHL is a prime candidate for genetic therapies due to the fact that PNSHL has been studied extensively, and there is a potentially wide window between identification of the disorder and the onset of hearing loss. Several gene therapy strategies exist that show potential for targeting PNSHL, including viral and non-viral approaches, and gene editing versus gene-modulating approaches. To fully explore the potential of these therapy strategies, a faithful in vitro model of the human inner ear is needed. Such models may come from induced pluripotent stem cells (iPSCs). The development of new treatment modalities by combining iPSC modeling with novel and innovative gene therapy approaches will pave the way for future applications leading to improved quality of life for many affected individuals and their families.

PMID:33507440 | DOI:10.1007/s10162-020-00781-0

SOURCE:
Journal of the Association for Research in Otolaryngology : JARO

PUBLISHER:

PMID:
pubmed:33507440

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33507440

DOI:
10.1007/s10162-020-00781-0

DATE – PUBLISHED:
Thu, 28 Jan 2021 06:00:00 -0500

DATE – DOI:
2021-01-28T16:56:11Z

DATE – ADDED:
01/28/21 11:57PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33507440/

LINK – DOI:
https://doi.org/10.1007/s10162-020-00781-0

LINK – PUBLISHER:
http://link.springer.com/10.1007/s10162-020-00781-0

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-01-29T04:57:19+00:00, https://www.hearinglosstreatmentreport.com.

Frequency Therapeutics appoints Chief Manufacturing Officer as it prepares for larger studies in support of lead FX-322 program

https://investors.frequencytx.com/news-releases/news-release-details/frequency-therapeutics-appoints-quentin-mccubbin-phd-chief

Frequency Therapeutics Appoints Quentin McCubbin, Ph.D., as Chief Manufacturing Officer
WOBURN, Mass.–(BUSINESS WIRE)–Jan. 19, 2021– Frequency Therapeutics, Inc. (Nasdaq: FREQ), a clinical-stage biotechnology company focused on harnessing the body’s innate biology to repair or reverse damage caused by a broad range of degenerative diseases, today announced the appointment of Quentin McCubbin, Ph.D., as chief manufacturing officer. Dr. McCubbin will oversee Company technical operations, leading drug product formulation, chemistry manufacturing and controls (CMC) and supply chain, to support the development of Frequency’s pipeline of product candidates.

Dr. McCubbin joins Frequency from Cerevel Therapeutics, a clinical-stage biotechnology company where he served as head of technical operations. Prior to Cerevel, he spent 19 years at Takeda/Millennium Pharmaceuticals in various roles progressing in responsibility, including six years as vice president of pharmaceutical sciences and global head of process chemistry.

“Quentin’s background and leadership in technical operations will be critical as we prepare for larger studies in support of our lead FX-322 program that aims to treat the most common form of hearing loss, and as we look to diversify and expand our clinical pipeline with a program for remyelination in multiple sclerosis,” sa

FX-322 in Adults With Severe Sensorineural Hearing Loss

CATEGORY:
Clinical Trials

TITLE:
FX-322 in Adults With Severe Sensorineural Hearing Loss

INTERVENTION/TREATMENT:

PHASE:

DESCRIPTION:
Conditions :   Hearing Loss, Sensorineural;   Noise Induced Hearing Loss;   Sudden Hearing Loss

Interventions :   Drug: FX-322;   Other: Placebo

Sponsor :   Frequency Therapeutics

Recruiting

ID:
NCT04629664

STATUS:

DATE – FIRST POSTED:
Mon, 16 Nov 2020 12:00:00 EST

DATE – LAST UPDATE POSTED:
11/16/20 07:07AM

DATE – RETRIEVED:
11/16/20 07:07AM

LINK – STUDY HISTORY:
https://clinicaltrials.gov/ct2/history/NCT04629664

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT04629664

Glucose Protects Cochlear Hair Cells Against Oxidative Stress and Attenuates Noise-Induced Hearing Loss in Mice

CATEGORY:
Research

SCREENSHOT:
Glucose Protects Cochlear Hair Cells Against Oxidative Stress and Attenuates Noise-Induced Hearing Loss in Mice Screenshot

TITLE:
Glucose Protects Cochlear Hair Cells Against Oxidative Stress and Attenuates Noise-Induced Hearing Loss in Mice

CONTENT:
Neurosci Bull. 2021 Jan 7. doi: 10.1007/s12264-020-00624-1. Online ahead of print.

ABSTRACT

Oxidative stress is the key determinant in the pathogenesis of noise-induced hearing loss (NIHL). Given that cellular defense against oxidative stress is an energy-consuming process, the aim of the present study was to investigate whether increasing energy availability by glucose supplementation protects cochlear hair cells against oxidative stress and attenuates NIHL. Our results revealed that glucose supplementation reduced the noise-induced formation of reactive oxygen species (ROS) and consequently attenuated noise-induced loss of outer hair cells, inner hair cell synaptic ribbons, and NIHL in CBA/J mice. In cochlear explants, glucose supplementation increased the levels of ATP and NADPH, as well as attenuating H2 O2 -induced ROS production and cytotoxicity. Moreover, pharmacological inhibition of glucose transporter type 1 activity abolished the protective effects of glucose against oxidative stress in HEI-OC1 cells. These findings suggest that energy availability is crucial for oxidative stress resistance and glucose supplementation offers a simple and effective approach for the protection of cochlear hair cells against oxidative stress and NIHL.

PMID:33415566 | DOI:10.1007/s12264-020-00624-1

SOURCE:
Neuroscience bulletin

PUBLISHER:

PMID:
pubmed:33415566

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33415566

DOI:
10.1007/s12264-020-00624-1

DATE – PUBLISHED:
Fri, 08 Jan 2021 06:00:00 -0500

DATE – DOI:
2021-01-07T18:43:13Z

DATE – ADDED:
01/08/21 01:01PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33415566/

LINK – DOI:
https://doi.org/10.1007/s12264-020-00624-1

LINK – PUBLISHER:
http://link.springer.com/10.1007/s12264-020-00624-1

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-01-08T18:01:22+00:00, https://www.hearinglosstreatmentreport.com.

Polymorphisms in the FAS gene are associated with susceptibility to noise-induced hearing loss

CATEGORY:
Research

SCREENSHOT:
Polymorphisms in the FAS gene are associated with susceptibility to noise-induced hearing loss Screenshot

TITLE:
Polymorphisms in the FAS gene are associated with susceptibility to noise-induced hearing loss

CONTENT:
Environ Sci Pollut Res Int. 2021 Jan 7. doi: 10.1007/s11356-020-12028-9. Online ahead of print.

ABSTRACT

This study investigated the relationship between genetic polymorphisms in the FAS gene and noise-induced hearing loss (NIHL) risk among Chinese workers exposed to occupational noise, and the molecular mechanism of NIHL caused by noise. In this case-control study, 692 NIHL workers and 650 controls were selected for genotyping of four single nucleotide polymorphisms (SNPs) of the FAS gene. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of the association of these genetic polymorphisms and NIHL. At the same time, a noise-exposed rat model was constructed to further clarify the effect of noise exposure on fas gene expression and the pathogenic mechanism of NIHL. Two polymorphisms, rs1468063 and rs2862833, were associated with NIHL in the case-control study. Individuals with the rs1468063-TT or rs2862833-AA genotypes had decreased NIHL risk (p < 0.01, p = 0.02, respectively). Compared with the control group, the hearing threshold of the case group of rats increased, while serum MDA, urine 8-OHdG, and fas gene expression increased, but let-7e expression decreased. Genetic polymorphisms in the FAS gene are related to the risk of NIHL in the Chinese population. Noise can cause a large amount of reactive oxygen species (ROS) in the cochlea tissue and blood, which lead to oxidative stress, lipid peroxidation, and DNA damage, further activating the FAS gene, and ultimately leading to hearing loss. PMID:33411277 | DOI:10.1007/s11356-020-12028-9 SOURCE: Environmental science and pollution research international PUBLISHER: PMID: pubmed:33411277 ID: 0b58ea4968e09ff10f4e1238c494f316pubmed:33411277 DOI: 10.1007/s11356-020-12028-9 DATE - PUBLISHED: Thu, 07 Jan 2021 06:00:00 -0500 DATE - DOI: 2021-01-07T08:06:27Z DATE - ADDED: 01/07/21 06:43PM LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33411277/ LINK - DOI: https://doi.org/10.1007/s11356-020-12028-9 LINK - PUBLISHER: http://link.springer.com/10.1007/s11356-020-12028-9 IMAGE: REFERENCE: Hearing Loss Treatment Report, Urgent Research, 2021-01-07T23:43:34+00:00, https://www.hearinglosstreatmentreport.com.

Sensorion Provides Update on Development of SENS-401 for Sudden Sensorineural Hearing Loss: Phase 2 topline results delayed, now expected in Q4 2021…

https://www.businesswire.com/news/home/20210104005852/en/Sensorion-Provides-an-Update-on-Plans-and-Progress-in-the-Development-of-SENS-401-for-the-Prevention-of-Hearing-Loss

Sensorion Provides an Update on Plans and Progress in the Development of SENS-401 for the Prevention of Hearing Loss
Clinical trial to treat patients suffering from Cisplatin Induced Ototoxicity (CIO) with SENS-401 expected to start in H2 2021
Natural history study in CIO expected to start in H1 2021 to generate data on disease evolution

Phase 2 topline results from SENS-401 study in SSNHL delayed further due to COVID-19 and now expected in Q4 2021

Therapeutic Application of Mesenchymal Stem Cells for Cochlear Regeneration

CATEGORY:
Research

SCREENSHOT:
Therapeutic Application of Mesenchymal Stem Cells for Cochlear Regeneration Screenshot

TITLE:
Therapeutic Application of Mesenchymal Stem Cells for Cochlear Regeneration

CONTENT:
In Vivo. 2021 Jan-Feb;35(1):13-22. doi: 10.21873/invivo.12227.

ABSTRACT

Hearing loss is one of the major worldwide health problems that seriously affects human social and cognitive development. In the auditory system, three components outer ear, middle ear and inner ear are essential for the hearing mechanism. In the inner ear, sensory hair cells and ganglion neuronal cells are the essential supporters for hearing mechanism. Damage to these cells can be caused by long-term exposure of excessive noise, ototoxic drugs (aminoglycosides), ear tumors, infections, heredity and aging. Since mammalian cochlear hair cells do not regenerate naturally, some therapeutic interventions may be required to replace the damaged or lost cells. Cochlear implants and hearing aids are the temporary solutions for people suffering from severe hearing loss. The current discoveries in gene therapy may provide a deeper understanding in essential genes for the inner ear regeneration. Stem cell migration, survival and differentiation to supporting cells, cochlear hair cells and spiral ganglion neurons are the important foundation in understanding stem cell therapy. Moreover, mesenchymal stem cells (MSCs) from different sources (bone marrow, umbilical cord, adipose tissue and placenta) could be used in inner ear therapy. Transplanted MSCs in the inner ear can recruit homing factors at the damaged sites to induce transdifferentiation into inner hair cells and ganglion neurons or regeneration of sensory hair cells, thus enhancing the cochlear function. This review summarizes the potential application of mesenchymal stem cells in hearing restoration and combining stem cell and molecular therapeutic strategies can also be used in the recovery of cochlear function.

PMID:33402445 | DOI:10.21873/invivo.12227

SOURCE:
In vivo (Athens, Greece)

PUBLISHER:

PMID:
pubmed:33402445

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33402445

DOI:
10.21873/invivo.12227

DATE – PUBLISHED:
Wed, 06 Jan 2021 06:00:00 -0500

DATE – DOI:
2021-01-05T18:16:14Z

DATE – ADDED:
01/06/21 06:28AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33402445/

LINK – DOI:
https://doi.org/10.21873/invivo.12227

LINK – PUBLISHER:
http://iv.iiarjournals.org/lookup/doi/10.21873/invivo.12227

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-01-06T11:28:12+00:00, https://www.hearinglosstreatmentreport.com.

Trk agonist drugs rescue noise-induced hidden hearing loss

CATEGORY:
Research

SCREENSHOT:
Trk agonist drugs rescue noise-induced hidden hearing loss Screenshot

TITLE:
Trk agonist drugs rescue noise-induced hidden hearing loss

CONTENT:
JCI Insight. 2020 Dec 29:142572. doi: 10.1172/jci.insight.142572. Online ahead of print.

ABSTRACT

TrkB agonist drugs are shown here to have a significant effect on the regeneration of afferent cochlear synapses after noise-induced synaptopathy. The effects were consistent with regeneration of cochlear synapses that we observed in vitro after synaptic loss due to kainic acid-induced glutamate toxicity and were elicited by administration of TrkB agonists, amitriptyline and 7,8- dihydroxyflavone, directly into the cochlea via the posterior semicircular canal 48 h after exposure to noise. Synaptic counts at the inner hair cell and wave 1 amplitudes in the ABR were partially restored 2 weeks after drug treatment. Effects of amitriptyline on wave 1 amplitude and afferent auditory synapse numbers in noise-exposed ears after systemic (as opposed to local) delivery were profound and long-lasting; synapses in the treated animals remained intact one year after the treatment. However, the effect of systemically delivered amitriptyline on synaptic rescue was dependent on dose and the time window of administration: it was only effective when given before noise exposure at the highest injected dose. The long-lasting effect and the efficacy of post-exposure treatment indicate a potential broad application for the treatment of synaptopathy, which often goes undetected until well after the original damaging exposure(s).

PMID:33373328 | DOI:10.1172/jci.insight.142572

SOURCE:
JCI insight

PUBLISHER:

PMID:
pubmed:33373328

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33373328

DOI:
10.1172/jci.insight.142572

DATE – PUBLISHED:
Tue, 29 Dec 2020 06:00:00 -0500

DATE – DOI:
2020-12-29T17:02:53Z

DATE – ADDED:
12/29/20 11:36PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33373328/

LINK – DOI:
https://doi.org/10.1172/jci.insight.142572

LINK – PUBLISHER:
http://insight.jci.org/articles/view/142572

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-30T04:36:21+00:00, https://www.hearinglosstreatmentreport.com.

Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo

CATEGORY:
Research

SCREENSHOT:
Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo Screenshot

TITLE:
Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo

CONTENT:
Clin Transl Med. 2020 Dec;10(8):e262. doi: 10.1002/ctm2.262.

ABSTRACT

The lack of approved anti-inflammatory and neuroprotective therapies in otology has been acknowledged in the last decades and recent approaches are heralding a new era in the field. Extracellular vesicles (EVs) derived from human multipotent (mesenchymal) stromal cells (MSC) can be enriched in vesicular secretome fractions, which have been shown to exert effects (eg, neuroprotection and immunomodulation) of their parental cells. Hence, MSC-derived EVs may serve as novel drug candidates for several inner ear diseases. Here, we provide first evidence of a strong neuroprotective potential of human stromal cell-derived EVs on inner ear physiology. In vitro, MSC-EV preparations exerted immunomodulatory activity on T cells and microglial cells. Moreover, local application of MSC-EVs to the inner ear significantly attenuated hearing loss and protected auditory hair cells from noise-induced trauma in vivo. Thus, EVs derived from the vesicular secretome of human MSC may represent a next-generation biological drug that can exert protective therapeutic effects in a complex and nonregenerating organ like the inner ear.

PMID:33377658 | DOI:10.1002/ctm2.262

SOURCE:
Clinical and translational medicine

PUBLISHER:

PMID:
pubmed:33377658

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33377658

DOI:
10.1002/ctm2.262

DATE – PUBLISHED:
Wed, 30 Dec 2020 06:00:00 -0500

DATE – DOI:
2020-12-22T14:56:50Z

DATE – ADDED:
12/30/20 05:51PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33377658/

LINK – DOI:
https://doi.org/10.1002/ctm2.262

LINK – PUBLISHER:
https://onlinelibrary.wiley.com/doi/10.1002/ctm2.262

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-30T22:51:39+00:00, https://www.hearinglosstreatmentreport.com.

Frequency Therapeutics to Host Investor Event on the Potential for Restorative Treatments for Acquired Sensorineural Hearing Loss

CATEGORY:
News, Companies, Press Releases

TAGS:
Frequency Therapeutics

TITLE:
Frequency Therapeutics to Host Investor Event on the Potential for Restorative Treatments for Acquired Sensorineural Hearing Loss

DESCRIPTION:
Event to be Held   January 19, 2021 at 8:00 am ET ; Will Feature Prominent Otolaryngology and Audiology Key Opinion Leaders Phase 2a Day-90 Readout for FX-322, Frequency’s Lead Product Candidate, for Acquired Sensorineural Hearing Loss Anticipated in Late Q1 2021; End of Study Readout in Late Q2

SOURCE:
Frequency Therapeutics

GUID:
aa0e5cd3eeeda8adba6fabfea4ff535c

ID:
b96d0a0b599e6d4315f064cd6ff0e099aa0e5cd3eeeda8adba6fabfea4ff535c

DATE – PUBLISHED:

DATE – FOUND:
12/18/20 08:22AM

LINK – PUBLISHER:
https://investors.frequencytx.com/news-releases/news-release-details/frequency-therapeutics-host-investor-event-potential-restorative/

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-18T13:22:17+00:00, https://www.hearinglosstreatmentreport.com.

Otonomy Reports Positive Top-Line Results from Phase 1/2 Clinical Trial of OTO-413 in Patients with Hearing Loss

https://investors.otonomy.com/news-releases/news-release-details/otonomy-reports-positive-top-line-results-phase-12-clinical-0

Otonomy Reports Positive Top-Line Results from Phase 1/2 Clinical Trial of OTO-413 in Patients with Hearing Loss
December 17, 2020 at 7:00 AM EST
OTO-413 demonstrated a higher proportion of responders than placebo based on multiple speech-in-noise hearing tests

Hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway

CATEGORY:
Research

SCREENSHOT:
Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway Screenshot

TITLE:
Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway

CONTENT:
Pflugers Arch. 2020 Dec 17. doi: 10.1007/s00424-020-02496-w. Online ahead of print.

ABSTRACT

Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly and constitutes the third highest risk factor for dementia. Lifetime noise exposure, genetic predispositions for degeneration, and metabolic stress are assumed to be the major causes of ARHL. Both noise-induced and hereditary progressive hearing have been linked to decreased cell surface expression and impaired conductance of the potassium ion channel KV 7.4 (KCNQ4) in outer hair cells, inspiring future therapies to maintain or prevent the decline of potassium ion channel surface expression to reduce ARHL. In concert with KV 7.4 in outer hair cells, KV 7.1 (KCNQ1) in the stria vascularis, calcium-activated potassium channels BK (KCNMA1) and SK2 (KCNN2) in hair cells and efferent fiber synapses, and KV 3.1 (KCNC1) in the spiral ganglia and ascending auditory circuits share an upregulated expression or subcellular targeting during final differentiation at hearing onset. They also share a distinctive fragility for noise exposure and age-dependent shortfalls in energy supply required for sustained surface expression. Here, we review and discuss the possible contribution of select potassium ion channels in the cochlea and auditory pathway to ARHL. We postulate genes, proteins, or modulators that contribute to sustained ion currents or proper surface expressions of potassium channels under challenging conditions as key for future therapies of ARHL.

PMID:33336302 | DOI:10.1007/s00424-020-02496-w

SOURCE:
Pflugers Archiv : European journal of physiology

PUBLISHER:

PMID:
pubmed:33336302

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33336302

DOI:
10.1007/s00424-020-02496-w

DATE – PUBLISHED:
Fri, 18 Dec 2020 06:00:00 -0500

DATE – DOI:
2020-12-17T23:03:30Z

DATE – ADDED:
12/18/20 11:55AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33336302/

LINK – DOI:
https://doi.org/10.1007/s00424-020-02496-w

LINK – PUBLISHER:
http://link.springer.com/10.1007/s00424-020-02496-w

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-18T16:55:45+00:00, https://www.hearinglosstreatmentreport.com.

Clinical Trial of FX-322 for Age-Related Hearing Loss Is Now ACTIVE

Study is no longer recruiting participants. 30 patients enrolled. Half will get a single dose of FX-322, other half will get a placebo. Estimated primary completion date: March 2021. Estimated study completion date: June 2021. Stay tuned…

Link to official study record (last update posted on December 16, 2020):

https://clinicaltrials.gov/ct2/show/NCT04601909

The other recently-added FX-322 study (for severe sensorineural hearing loss) is expected to start before the end of the year, according to a November 16 press release from Frequency Therapeutics.

More updates to follow. Remember to subscribe to the email newsletter, which will begin sending soon. Email michael@urgentresearch.com if you have any comments or feedback.

FX-322 in Adults With Age-Related Sensorineural Hearing Loss

CATEGORY:
Clinical Trials

TITLE:
FX-322 in Adults With Age-Related Sensorineural Hearing Loss

INTERVENTION/TREATMENT:

PHASE:

DESCRIPTION:
Conditions :   Presbycusis;   Hearing Loss, Sensorineural;   Noise Induced Hearing Loss;   Sudden Hearing Loss

Interventions :   Drug: FX-322;   Other: placebo

Sponsor :   Frequency Therapeutics

Recruiting

ID:
NCT04601909

STATUS:

DATE – FIRST POSTED:
Mon, 26 Oct 2020 12:00:00 EDT

DATE – LAST UPDATE POSTED:
10/26/20 07:11AM

DATE – RETRIEVED:
10/26/20 07:11AM

LINK – STUDY HISTORY:
https://clinicaltrials.gov/ct2/history/NCT04601909

LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT04601909

Sonova Invests €5 Million in Sensorion [SENS-401] as the Companies Plan a Collaboration in Hearing Loss

https://www.businesswire.com/news/home/20201214005892/en/Sonova-Invests-%E2%82%AC5-Million-in-Sensorion-as-the-Companies-Plan-a-Collaboration-in-Hearing-Loss

Sonova Invests €5 Million in Sensorion as the Companies Plan a Collaboration in Hearing Loss
Sonova invests at €1.70 per share, to hold circa 3.7% stake in Sensorion
Companies signed a letter of intent relating to a collaboration to develop new solutions for hearing loss

The Role of FoxG1 in the Inner Ear

https://www.frontiersin.org/articles/10.3389/fcell.2020.614954/full

REVIEW ARTICLE
Front. Cell Dev. Biol., 03 December 2020 | https://doi.org/10.3389/fcell.2020.614954
The Role of FoxG1 in the Inner Ear

Weakening of Interaction Networks with Aging in Tip-Link Protein Induces Hearing Loss

CATEGORY:
Research

SCREENSHOT:
Weakening of Interaction Networks with Aging in Tip-Link Protein Induces Hearing Loss Screenshot

TITLE:
Weakening of Interaction Networks with Aging in Tip-Link Protein Induces Hearing Loss

CONTENT:
Biochem J. 2020 Dec 3:BCJ20200799. doi: 10.1042/BCJ20200799. Online ahead of print.

ABSTRACT

Age-related hearing loss (ARHL) is a common condition in humans marking the gradual decrease in hearing with age. Perturbations in the tip-link protein cadherin-23 that absorbs the mechanical tension from sound and maintains the integrity of hearing is associated with ARHL. Here, in search of molecular origins for ARHL, we dissect the conformational behavior of cadherin-23 along with the mutant S47P that progresses the hearing-loss drastically. Using an array of experimental and computational approaches, we highlight a lower thermodynamic stability, significant weakening in the hydrogen-bond network and inter-residue correlations among β-strands, due to the S47P mutation. The loss in correlated motions translates to not only a remarkable two orders of magnitude slower folding in the mutant but also to a proportionately complex unfolding mechanism. We thus propose that loss in correlated motions within cadherin-23 with aging may trigger ARHL, a molecular feature that likely holds true for other disease-mutations in β-strand-rich proteins.

PMID:33270084 | DOI:10.1042/BCJ20200799

SOURCE:
The Biochemical journal

PUBLISHER:

PMID:
pubmed:33270084

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33270084

DOI:
10.1042/BCJ20200799

DATE – PUBLISHED:
Thu, 03 Dec 2020 06:00:00 -0500

DATE – DOI:
2020-12-03T14:31:41Z

DATE – ADDED:
12/03/20 08:09PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33270084/

LINK – DOI:
https://doi.org/10.1042/BCJ20200799

LINK – PUBLISHER:
https://portlandpress.com/biochemj/article/doi/10.1042/BCJ20200799/227128/Weakening-of-Interaction-Networks-with-Aging-in

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-04T01:09:05+00:00, https://www.hearinglosstreatmentreport.com.

BRAF inhibition protects against hearing loss in mice

CATEGORY:
Research

SCREENSHOT:
BRAF inhibition protects against hearing loss in mice Screenshot

TITLE:
BRAF inhibition protects against hearing loss in mice

CONTENT:
Sci Adv. 2020 Dec 2;6(49):eabd0561. doi: 10.1126/sciadv.abd0561. Print 2020 Dec.

ABSTRACT

Hearing loss caused by noise, aging, antibiotics, and chemotherapy affects 10% of the world population, yet there are no Food and Drug Administration (FDA)-approved drugs to prevent it. Here, we screened 162 small-molecule kinase-specific inhibitors for reduction of cisplatin toxicity in an inner ear cell line and identified dabrafenib (TAFINLAR), a BRAF kinase inhibitor FDA-approved for cancer treatment. Dabrafenib and six additional kinase inhibitors in the BRAF/MEK/ERK cellular pathway mitigated cisplatin-induced hair cell death in the cell line and mouse cochlear explants. In adult mice, oral delivery of dabrafenib repressed ERK phosphorylation in cochlear cells, and protected from cisplatin- and noise-induced hearing loss. Full protection was achieved in mice with co-treatment with oral AZD5438, a CDK2 kinase inhibitor. Our study explores a previously unidentified cellular pathway and molecular target BRAF kinase for otoprotection and may advance dabrafenib into clinics to benefit patients with cisplatin- and noise-induced ototoxicity.

PMID:33268358 | DOI:10.1126/sciadv.abd0561

SOURCE:
Science advances

PUBLISHER:

PMID:
pubmed:33268358

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33268358

DOI:
10.1126/sciadv.abd0561

DATE – PUBLISHED:
Thu, 03 Dec 2020 06:00:00 -0500

DATE – DOI:
2020-12-03T02:03:28Z

DATE – ADDED:
12/03/20 07:55AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33268358/

LINK – DOI:
https://doi.org/10.1126/sciadv.abd0561

LINK – PUBLISHER:
https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.abd0561

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-03T12:55:04+00:00, https://www.hearinglosstreatmentreport.com.

Mutations of MAP1B encoding a microtubule-associated phosphoprotein cause sensorineural hearing loss

CATEGORY:
Research

SCREENSHOT:
Mutations of MAP1B encoding a microtubule-associated phosphoprotein cause sensorineural hearing loss Screenshot

TITLE:
Mutations of MAP1B encoding a microtubule-associated phosphoprotein cause sensorineural hearing loss

CONTENT:
JCI Insight. 2020 Dec 3;5(23):136046. doi: 10.1172/jci.insight.136046.

ABSTRACT

The pathophysiology underlying spiral ganglion cell defect-induced deafness remains elusive. Using the whole exome sequencing approach, in combination with functional assays and a mouse disease model, we identified the potentially novel deafness-causative MAP1B gene encoding a highly conserved microtubule-associated protein. Three novel heterozygous MAP1B mutations (c.4198A>G, p.1400S>G; c.2768T>C, p.923I>T; c.5512T>C, p.1838F>L) were cosegregated with autosomal dominant inheritance of nonsyndromic sensorineural hearing loss in 3 unrelated Chinese families. Here, we show that MAP1B is highly expressed in the spiral ganglion neurons in the mouse cochlea. Using otic sensory neuron-like cells, generated by pluripotent stem cells from patients carrying the MAP1B mutation and control subject, we demonstrated that the p.1400S>G mutation caused the reduced levels and deficient phosphorylation of MAP1B, which are involved in the microtubule stability and dynamics. Strikingly, otic sensory neuron-like cells exhibited disturbed dynamics of microtubules, axonal elongation, and defects in electrophysiological properties. Dysfunctions of these derived otic sensory neuron-like cells were rescued by genetically correcting MAP1B mutation using CRISPR/Cas9 technology. Involvement of MAP1B in hearing was confirmed by audiometric evaluation of Map1b heterozygous KO mice. These mutant mice displayed late-onset progressive sensorineural hearing loss that was more pronounced in the high frequencies. The spiral ganglion neurons isolated from Map1b mutant mice exhibited the deficient phosphorylation and disturbed dynamics of microtubules. Map1b deficiency yielded defects in the morphology and electrophysiology of spiral ganglion neurons, but it did not affect the morphologies of cochlea in mice. Therefore, our data demonstrate that dysfunctions of spiral ganglion neurons induced by MAP1B deficiency caused hearing loss.

PMID:33268592 | DOI:10.1172/jci.insight.136046

SOURCE:
JCI insight

PUBLISHER:

PMID:
pubmed:33268592

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33268592

DOI:
10.1172/jci.insight.136046

DATE – PUBLISHED:
Thu, 03 Dec 2020 06:00:00 -0500

DATE – DOI:
2020-12-02T16:04:40Z

DATE – ADDED:
12/03/20 07:55AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33268592/

LINK – DOI:
https://doi.org/10.1172/jci.insight.136046

LINK – PUBLISHER:
https://insight.jci.org/articles/view/136046

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-03T12:55:03+00:00, https://www.hearinglosstreatmentreport.com.

Noise Exposures Causing Hearing Loss Generate Proteotoxic Stress and Activate the Proteostasis Network

CATEGORY:
Research

TITLE:
Noise Exposures Causing Hearing Loss Generate Proteotoxic Stress and Activate the Proteostasis Network

DESCRIPTION:
Exposure to excessive sound causes noise-induced hearing loss through complex mechanisms and represents a common and unmet neurological condition. We investigate how noise insults affect the cochlea with proteomics and functional assays. Quantitative proteomics reveals that exposure to loud noise causes proteotoxicity. We identify and confirm hundreds of proteins that accumulate, including cytoskeletal proteins, and several nodes of the proteostasis network. Transcriptomic analysis reveals that…

CONTENT:
Cell Rep. 2020 Nov 24;33(8):108431. doi: 10.1016/j.celrep.2020.108431.

ABSTRACT

Exposure to excessive sound causes noise-induced hearing loss through complex mechanisms and represents a common and unmet neurological condition. We investigate how noise insults affect the cochlea with proteomics and functional assays. Quantitative proteomics reveals that exposure to loud noise causes proteotoxicity. We identify and confirm hundreds of proteins that accumulate, including cytoskeletal proteins, and several nodes of the proteostasis network. Transcriptomic analysis reveals that a subset of the genes encoding these proteins also increases acutely after noise exposure, including numerous proteasome subunits. Global cochlear protein ubiquitylation levels build up after exposure to excess noise, and we map numerous posttranslationally modified lysines residues. Several collagen proteins decrease in abundance, and Col9a1 specifically localizes to pillar cell heads. After two weeks of recovery, the cochlea selectively elevates the abundance of the protein synthesis machinery. We report that overstimulation of the auditory system drives a robust cochlear proteotoxic stress response.

PMID:33238128 | DOI:10.1016/j.celrep.2020.108431

SOURCE:
Cell reports

DATE – PUBLISHED:
24 Nov 2020

DATE – ADDED:
Wed, 25 Nov 2020 06:00:00 -0500

DATE – FOUND:
11/26/20 05:57AM

PUBMED ID:
pubmed:33238128

DOI:
10.1016/j.celrep.2020.108431

PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33238128/

DOI LINK:
https://doi.org/10.1016/j.celrep.2020.108431

PUBLISHER LINK:
https://linkinghub.elsevier.com/retrieve/pii/S2211124720314200

JOURNAL LINK:
https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31420-0

Upcoming Webinar from the Hearing Medicines Discovery Syndicate: “How and Why” to Commercialise your Hearing Research (Nov 26)

https://go.md.catapult.org.uk/how-why-commercialise-hearing-research/

The Emerging Hearing Medicines Landscape

A monthly webinar series developed by the Hearing Medicines Discovery Syndicate, exploring hearing drug discovery in the context of an emerging area for medicines development and a growing market.

Through this series of webinars, we will explore the emerging hearing medicines landscape by inviting leading clinicians, academics and industry representatives along with people with lived experience of hearing loss, to share their expertise and insight.

Over 4 webinars we will provide a 360-view of the field covering the patient need, the key challenges faced by innovators, how to commercialise your hearing research and why regenerative approaches could be a game-changer for hearing medicines discovery.

Endoscopic-Assisted Drug Delivery for Inner Ear Regeneration

TITLE:
Endoscopic-Assisted Drug Delivery for Inner Ear Regeneration

DESCRIPTION:
Sensorineural hearing loss is caused by irreversible loss of auditory hair cells and/or neurons and is increasing in prevalence. Hair cells and neurons do not regenerate after damage, but novel regeneration therapies based on small molecule drugs, gene therapy, and cell replacement strategies offer promising therapeutic options. Endogenous and exogenous regeneration techniques are discussed in context of their feasibility for hair cell and neuron regeneration. Gene therapy and treatment of…

CONTENT:
Otolaryngol Clin North Am . 2021 Feb;54(1):189-200. doi: 10.1016/j.otc.2020.09.022.

ABSTRACT

Sensorineural hearing loss is caused by irreversible loss of auditory hair cells and/or neurons and is increasing in prevalence. Hair cells and neurons do not regenerate after damage, but novel regeneration therapies based on small molecule drugs, gene therapy, and cell replacement strategies offer promising therapeutic options. Endogenous and exogenous regeneration techniques are discussed in context of their feasibility for hair cell and neuron regeneration. Gene therapy and treatment of synaptopathy represent promising future therapies. Minimally invasive endoscopic ear surgery offers a viable approach to aid in delivery of pharmacologic compounds, cells, or viral vectors to the inner ear for all of these techniques.

PMID:33243375 | DOI:10.1016/j.otc.2020.09.022

IDENTIFIER:
pmid:33243375,doi:10.1016/j.otc.2020.09.022

PMID:
pubmed:33243375

ID:
5aa6076e0127310720e03f8fa09545b5pubmed:33243375

DOI:
10.1016/j.otc.2020.09.022

DATE – PUBLISHED:
Fri, 27 Nov 2020 06:00:00 -0500

DATE – DOI:
2020-11-23T09:13:42Z

DATE – RETRIEVED:
11/27/20 06:17AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33243375/

LINK – DOI:
https://doi.org/10.1016/j.otc.2020.09.022

LINK – PUBLISHER:
https://linkinghub.elsevier.com/retrieve/pii/S0030666520366962

G6PD overexpression protects from oxidative stress and age-related hearing loss

CATEGORY:
Research

TITLE:
G6PD overexpression protects from oxidative stress and age-related hearing loss

DESCRIPTION:
Aging of the auditory system is associated with the incremental production of reactive oxygen species (ROS) and the accumulation of oxidative damage in macromolecules, which contributes to cellular malfunction, compromises cell viability, and, ultimately, leads to functional decline. Cellular detoxification relies in part on the production of NADPH, which is an important cofactor for major cellular antioxidant systems. NADPH is produced principally by the housekeeping enzyme glucose-6-phosphate…

CONTENT:
Aging Cell. 2020 Nov 22:e13275. doi: 10.1111/acel.13275. Online ahead of print.

ABSTRACT

Aging of the auditory system is associated with the incremental production of reactive oxygen species (ROS) and the accumulation of oxidative damage in macromolecules, which contributes to cellular malfunction, compromises cell viability, and, ultimately, leads to functional decline. Cellular detoxification relies in part on the production of NADPH, which is an important cofactor for major cellular antioxidant systems. NADPH is produced principally by the housekeeping enzyme glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the rate-limiting step in the pentose phosphate pathway. We show here that G6PD transgenic mice (G6PD-Tg), which show enhanced constitutive G6PD activity and NADPH production along life, have lower auditory thresholds than wild-type mice during aging, together with preserved inner hair cell (IHC) and outer hair cell (OHC), OHC innervation, and a conserved number of synapses per IHC. Gene expression of antioxidant enzymes was higher in 3-month-old G6PD-Tg mice than in wild-type counterparts, whereas the levels of pro-apoptotic proteins were lower. Consequently, nitration of proteins, mitochondrial damage, and TUNEL+ apoptotic cells were all lower in 9-month-old G6PD-Tg than in wild-type counterparts. Unexpectedly, G6PD overexpression triggered low-grade inflammation that was effectively resolved in young mice, as shown by the absence of cochlear cellular damage and macrophage infiltration. Our results lead us to propose that NADPH overproduction from an early stage is an efficient mechanism to maintain the balance between the production of ROS and cellular detoxification power along aging and thus prevents hearing loss progression.

PMID:33222382 | DOI:10.1111/acel.13275

SOURCE:
Aging cell

DATE – PUBLISHED:
22 Nov 2020

DATE – ADDED:
Sun, 22 Nov 2020 06:00:00 -0500

DATE – FOUND:
11/23/20 05:39AM

PUBMED ID:
pubmed:33222382

DOI:
10.1111/acel.13275

PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33222382/

DOI LINK:
https://doi.org/10.1111/acel.13275

PUBLISHER LINK:
https://onlinelibrary.wiley.com/doi/10.1111/acel.13275

Towards personalized auditory models: predicting individual sensorineural-hearing-loss profiles from recorded human auditory physiology [Preprint]

https://www.biorxiv.org/content/10.1101/2020.11.17.387001v1

https://www.biorxiv.org/content/10.1101/2020.11.17.387001v1?utm_source=hearinglosstreatmentreport.com

Towards personalized auditory models: predicting individual sensorineural-hearing-loss profiles from recorded human auditory physiology

Sarineh Keshishzadeh, Markus Garrett, Sarah Verhulst

doi: https://doi.org/10.1101/2020.11.17.387001

Frequency Therapeutics adds YET ANOTHER new FX-322 clinical trial… for SEVERE sensorineural hearing loss

Added today: A Phase 1b, Prospective, Randomized, Double-Blind, Placebo- Controlled, Single-Dose, Multicenter, Safety Study of FX-322 Administered by Intratympanic Injection in Adults With Severe Sensorineural Hearing Loss.

This is a Phase 1b placebo-controlled, double-blind, single-dose safety study of intratympanic FX-322 dosed in subjects with severe sensorineural hearing loss.

Approximately 30 subjects are planned to be enrolled in this study. The subjects will be randomized to receive one dose FX-322 (24) or placebo (6) and will return for safety, otologic, and audiologic assessments at Days 30 and 90 after the study injection.

What makes this new FX-322 trial different (compared to the trial that was added last month)?

This new study is for severe sensorineural hearing loss (previously added study is for age-related hearing loss). The inclusion criteria requires a “pure tone average of “26-70 dB at 500Hz, 1000Hz, 2000Hz, and 4000Hz at screening in the ear to be injected.”

Does it include a Tinnitus Assessment as a secondary outcome measure?

Yes.

Measured by the Tinnitus Functional Index (TFI), with a scale ranging from 0 to 100 that defines severity categories based on 25 self-reported answers.

What else? More fun facts:

Study is Recruiting and will enroll 30 participants. It does involve a placebo group however the ratio is 4:1 which means most (24) of the participants will get FX-322.

If you like those odds, here are the states where clinical trial sites are located:

  • Florida
  • Nebraska
  • New York
  • Texas
  • Virginia

Could more locations be added?

Very possible. We will post an update if/when more sites are added.

Here is the official link to the study:

https://clinicaltrials.gov/ct2/show/NCT04629664

More FX-322 updates:

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Single and dual vector gene therapy with AAV9-PHP.B rescues hearing in Tmc1 mutant mice

CATEGORY:
Research

TITLE:
Single and dual vector gene therapy with AAV9-PHP.B rescues hearing in Tmc1 mutant mice

DESCRIPTION:
AAV-mediated gene therapy is a promising approach for treating genetic hearing loss. Replacement or editing of the Tmc1 gene, encoding hair cell mechanosensory ion channels, is effective for hearing restoration in mice with some limitations. Efficient rescue of outer hair cell function, as well as lack of hearing recovery with later stage treatment, remain issues to be solved. Exogenous genes delivered with the AAV9-PHP.B capsid via the utricle transduce both inner and outer hair cells of the…

CONTENT:
Mol Ther. 2020 Nov 16:S1525-0016(20)30614-6. doi: 10.1016/j.ymthe.2020.11.016. Online ahead of print.

ABSTRACT

AAV-mediated gene therapy is a promising approach for treating genetic hearing loss. Replacement or editing of the Tmc1 gene, encoding hair cell mechanosensory ion channels, is effective for hearing restoration in mice with some limitations. Efficient rescue of outer hair cell function, as well as lack of hearing recovery with later stage treatment, remain issues to be solved. Exogenous genes delivered with the AAV9-PHP.B capsid via the utricle transduce both inner and outer hair cells of the mouse cochlea with high efficacy. Here we demonstrate that AAV9-PHP.B gene therapy can promote hair cell survival and successfully rescues hearing in three distinct mouse models of hearing loss. Tmc1 replacement with AAV9-PHP.B in a Tmc1 knockout mouse rescues hearing and promotes hair cell survival with equal efficacy in inner and outer hair cells. The same treatment in a recessive Tmc1 hearing loss model, Baringo, partially recovers hearing even with later stage treatment. Finally, dual delivery of SpCas9 and gRNA in separate AAV9-PHP.B vectors selectively disrupts a dominant Tmc1 allele and preserves hearing in Beethoven mice, a model of dominant, progressive hearing loss. Tmc1-targeted gene therapies using single or dual AAV9-PHP.B vectors offer potent and versatile approaches for treating dominant and recessive deafness.

PMID:33212302 | DOI:10.1016/j.ymthe.2020.11.016

SOURCE:
Molecular therapy : the journal of the American Society of Gene Therapy

DATE – PUBLISHED:
16 Nov 2020

DATE – ADDED:
Thu, 19 Nov 2020 06:00:00 -0500

DATE – FOUND:
11/20/20 05:29AM

PUBMED ID:
pubmed:33212302

DOI:
10.1016/j.ymthe.2020.11.016

PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33212302/

DOI LINK:
https://doi.org/10.1016/j.ymthe.2020.11.016

PUBLISHER LINK:
https://linkinghub.elsevier.com/retrieve/pii/S1525001620306146

Access to the Apical Cochlear Modiolus for Possible Stem Cell-Based and Gene Therapy of the Auditory Nerve

https://journals.lww.com/otology-neurotology/Abstract/9000/Access_to_the_Apical_Cochlear_Modiolus_for.95934.aspx

Access to the Apical Cochlear Modiolus for Possible Stem Cell-Based and Gene Therapy of the Auditory Nerve
Wrobel, Christian*,†; Bevis, Nicholas F.*; Meyer, Alexander C.*; Beutner, Dirk*Author Information
Otology & Neurotology: November 06, 2020 – Volume Publish Ahead of Print – Issue –
doi: 10.1097/MAO.0000000000002941

Efficacy of SENS-401 in Subjects With Severe or Profound Sudden Sensorineural Hearing Loss

https://clinicaltrials.gov/ct2/show/NCT03603314?type=Intr&cond=Hearing+Loss&lupd_s=05%2F05%2F2020&lupd_d=14&sort=nwst

Condition :   Severe Sudden Sensorineural Hearing Loss

Interventions :   Drug: SENS-401;   Other: Placebo Oral Tablet

Sponsor :   Sensorion

Recruiting

Efficacy of SENS 401 in Subjects With Severe or Profound Sudden Sensorineural Hearing Loss

NCT03603314

Fri, 27 Jul 2018 12:00:00 EDT

Last Update Posted: 05/19/20 06:40AM

Protection of Cochlear Ribbon Synapses and Prevention of Hidden Hearing Loss

CATEGORY:
Research

TITLE:
Protection of Cochlear Ribbon Synapses and Prevention of Hidden Hearing Loss

DESCRIPTION:
In the auditory system, ribbon synapses are vesicle-associated structures located between inner hair cells (IHCs) and spiral ganglion neurons that are implicated in the modulation of trafficking and fusion of synaptic vesicles at the presynaptic terminals. Synapse loss may result in hearing loss and difficulties with understanding speech in a noisy environment. This phenomenon happens without permanent hearing loss; that is, the cochlear synaptopathy is “hidden.” Recent studies have reported…

DATE – PUBLISHED:
Mon, 02 Nov 2020 22:35:10 +0000

LINK – PUBLISHER:
https://www.hindawi.com/journals/np/2020/8815990/

Frequency Therapeutics Announces Expanded FX-322 Clinical Development Program and Upcoming Day-90 Phase 2a Analysis

https://investors.frequencytx.com/news-releases/news-release-details/frequency-therapeutics-announces-expanded-fx-322-clinical

Frequency Therapeutics Announces Expanded FX-322 Clinical Development Program and Upcoming Day-90 Phase 2a Analysis
Company Will Report Data from Phase 2a Sensorineural Hearing Loss (SNHL) Study in Late Q1 2021

First Patient Dosed in Phase 1b Study of Age-Related Hearing Loss; Additional Phase 1b Study for Severe SNHL Patients to Start This Quarter

BDNF Outperforms TrkB Agonist 7,8,3′-THF in Preserving the Auditory Nerve in Deafened Guinea Pigs

CATEGORY:
Research

TITLE:
BDNF Outperforms TrkB Agonist 7,8,3′-THF in Preserving the Auditory Nerve in Deafened Guinea Pigs

DESCRIPTION:
In deaf subjects using a cochlear implant (CI) for hearing restoration, the auditory nerve is subject to degeneration, which may negatively impact CI effectiveness. This nerve degeneration can be reduced by neurotrophic treatment. Here, we compare the preservative effects of the naturally occurring tyrosine receptor kinase B (TrkB) agonist brain-derived neurotrophic factor (BDNF) and the small-molecule TrkB agonist 7,8,3′-trihydroxyflavone (THF) on the auditory nerve in deafened guinea pigs. THF…

CONTENT:
Brain Sci. 2020 Oct 28;10(11):E787. doi: 10.3390/brainsci10110787.

ABSTRACT

In deaf subjects using a cochlear implant (CI) for hearing restoration, the auditory nerve is subject to degeneration, which may negatively impact CI effectiveness. This nerve degeneration can be reduced by neurotrophic treatment. Here, we compare the preservative effects of the naturally occurring tyrosine receptor kinase B (TrkB) agonist brain-derived neurotrophic factor (BDNF) and the small-molecule TrkB agonist 7,8,3′-trihydroxyflavone (THF) on the auditory nerve in deafened guinea pigs. THF may be more effective than BDNF throughout the cochlea because of better pharmacokinetic properties. The neurotrophic compounds were delivered by placement of a gelatin sponge on the perforated round window membrane. To complement the histology of spiral ganglion cells (SGCs), electrically evoked compound action potential (eCAP) recordings were performed four weeks after treatment initiation. We analyzed the eCAP inter-phase gap (IPG) effect and measures derived from pulse-train evoked eCAPs, both indicative of SGC healthiness. BDNF but not THF yielded a significantly higher survival of SGCs in the basal cochlear turn than untreated controls. Regarding IPG effect and pulse-train responses, the BDNF-treated animals exhibited more normal responses than both untreated and THF-treated animals. We have thus confirmed the protective effect of BDNF, but we have not confirmed previously reported protective effects of THF with our clinically applicable delivery method.

PMID:33126525 | DOI:10.3390/brainsci10110787

SOURCE:
Brain sciences

DATE – PUBLISHED:
28 Oct 2020

DATE – ADDED:
Sat, 31 Oct 2020 06:00:00 -0400

DATE – FOUND:
10/31/20 12:11PM

PUBMED ID:
pubmed:33126525

DOI:
10.3390/brainsci10110787

PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33126525/

DOI LINK:
https://doi.org/10.3390/brainsci10110787

PUBLISHER LINK:
https://www.mdpi.com/2076-3425/10/11/787

Outcome of otolith organ function after treatment of sudden sensorineural hearing loss

CATEGORY:
Research

SCREENSHOT:
Outcome of otolith organ function after treatment of sudden sensorineural hearing loss Screenshot

TITLE:
Outcome of otolith organ function after treatment of sudden sensorineural hearing loss

CONTENT:
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Nov;34(11):993-998. doi: 10.13201/j.issn.2096-7993.2020.11.008.

ABSTRACT

Objective: This study aimed to assess the clinical practice value of ocular vestibular evoked myogenic potential（oVEMP） and cervical vestibular evoked myogenic potential（cVEMP） in monitoring the rehabilitation of vestibular function in patients with suddensen sorineural hearing loss（SSHL）. Method: Twenty-four patients with SSHL were retrospectively enrolled， showing no VEMP response on the affected side but exhibiting VEMP responses after therapies We analyzed the improvement and the restoration of hearing and the parameters of VEMP response. Result: After treatment, seven patients showed VEMP recovery, including three cases with both oVEMP and cVEMP recovery, three cases with oVEMP recovery, and one case with cVEMP recovery. Between VEMP recoved group and VEMP unrecoved group, before treatment, no significant difference was found in the thresholds of pure-tone audiometry（PTA）. However, after treatment, VEMP recoved group exhibited lower PTA thresholds and better PTA shift （P <0.01）. Multivariate analysis revealed that recovery of VEMP was the independent risk factor for the therapeutic effect of SSHL. Conclusion: The Combination of oVEMP and cVEMP is an objective tool for assessing vestibular otolithic end organ function during dynamic functional recovery in SSHL and the recovery of VEMP could predict the auditory improvement. PMID:33254317 | DOI:10.13201/j.issn.2096-7993.2020.11.008 SOURCE: Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery PUBLISHER: 突发性聋治疗后耳石器功能转归 PMID: pubmed:33254317 ID: 0b58ea4968e09ff10f4e1238c494f316pubmed:33254317 DOI: 10.13201/j.issn.2096-7993.2020.11.008 DATE - PUBLISHED: Mon, 30 Nov 2020 06:00:00 -0500 DATE - DOI: 2020-10-27T07:21:43Z DATE - ADDED: 12/01/20 05:32AM LINK - PUBMED: https://pubmed.ncbi.nlm.nih.gov/33254317/ LINK - DOI: https://doi.org/10.13201/j.issn.2096-7993.2020.11.008 LINK - PUBLISHER: http://kns.cnki.net/kcms/detail/detail.aspx?doi=10.13201/j.issn.2096-7993.2020.11.008 IMAGE: https://piccache.cnki.net/kdn/index/kns7/nimages/logo_xl.png https://kns.cnki.net/kcms/Detail/resource/gb/images/icon-qrcode-download.jpg,https://kns.cnki.net/kcms/Detail/resource/gb/images/icon-pop-sample.jpg,https://piccache.cnki.net/kdn/index/kns7/nimages/logo_xl.png,https://piccache.cnki.net/kdn/index/kns7/nimages/logo_tx.png,https://piccache.cnki.net/kdn/index/kns7/nimages/foot-logo.png,https://piccache.cnki.net/kdn/index/kns7/nimages/kxwz.jpg REFERENCE: Hearing Loss Treatment Report, Urgent Research, 2020-12-01T10:32:34+00:00, https://www.hearinglosstreatmentreport.com.

Analysis of related factors between sudden sensorineural hearing loss and serum indices base on artificial intelligence and big data

CATEGORY:
Research

SCREENSHOT:
Analysis of related factors between sudden sensorineural hearing loss and serum indices base on artificial intelligence and big data Screenshot

TITLE:
Analysis of related factors between sudden sensorineural hearing loss and serum indices base on artificial intelligence and big data

CONTENT:
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Nov;34(11):977-980. doi: 10.13201/j.issn.2096-7993.2020.11.004.

ABSTRACT

Objective: The etiology and pathophysiologic mechanism of sudden sensorineural hearing loss are undefined. We will use artificial intelligence and big data methods to explore the correlation between sudden sensorineural hearing loss and serum indices. Method: A total of 1218 patients with sudden deafness admitted to Sun Yat-sen Memorial Hospital were selected as the experimental group, 95 861 healthy subjects were randomly selected as the control group at the same period. Serum biochemical indexes in two groups were collected and analyzed by TreeNet and CART machine learning algorithms, to screen out highly correlated indicators with sudden sensorineural hearing loss and dig out a set of clinical features for people with high risk of sudden sensorineural hearing loss. Result: It was found that high prevalence rate of sudden sensorineural hearing loss is related to eosinophils, reticulocyte and fibrinogen. The areas under the receiver operator characteristic curves（ROC-AUC） were exploited to evaluate the prediction performance of TreeNet model. Overall the TreeNet model has provided high predictive ability by ROC curve, achieving AUC of 0.99, both recall and accuracy rate of 99.90%. Conclusion: There is significant difference between sudden deadness and normal people in serum biochemical indexes. Eosinophil is the first important indicator to distinguish sudden sensorineural hearing loss. Treenet model has important referenced significance for the screening and diagnosis of sudden sensorineural hearing loss.

PMID:33254313 | DOI:10.13201/j.issn.2096-7993.2020.11.004

SOURCE:
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery

PUBLISHER:
基于人工智能下突发性聋与血清指标的相关因素分析

PMID:
pubmed:33254313

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:33254313

DOI:
10.13201/j.issn.2096-7993.2020.11.004

DATE – PUBLISHED:
Mon, 30 Nov 2020 06:00:00 -0500

DATE – DOI:
2020-10-27T07:21:43Z

DATE – ADDED:
12/01/20 05:32AM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/33254313/

LINK – DOI:
https://doi.org/10.13201/j.issn.2096-7993.2020.11.004

LINK – PUBLISHER:
http://kns.cnki.net/kcms/detail/detail.aspx?doi=10.13201/j.issn.2096-7993.2020.11.004

IMAGE:
https://piccache.cnki.net/kdn/index/kns7/nimages/logo_xl.png

https://kns.cnki.net/kcms/Detail/resource/gb/images/icon-qrcode-download.jpg,https://kns.cnki.net/kcms/Detail/resource/gb/images/icon-pop-sample.jpg,https://piccache.cnki.net/kdn/index/kns7/nimages/logo_xl.png,https://piccache.cnki.net/kdn/index/kns7/nimages/logo_tx.png,https://piccache.cnki.net/kdn/index/kns7/nimages/foot-logo.png,https://piccache.cnki.net/kdn/index/kns7/nimages/kxwz.jpg

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2020-12-01T10:32:32+00:00, https://www.hearinglosstreatmentreport.com.

SENS-401 Phase 2 trial results expected in mid-2021, prelinical data expected by end of 2020

https://www.businesswire.com/news/home/20201020006234/en/Sensorion-reports-2020-first-half-results

Preclinical data from these studies are expected by the end of 2020.

Sensorion reports 2020 first half results
Financial position strengthened with €31m (US$36.5m) capital raise in September 2020

Gene therapy agreement expands pipeline and preclinical data
SENS-401 Phase II trial progressing with results expected in mid-2021
Cash position of €30.7m as of June 30, 2020, further reinforced by September capital raise
Cash runway now extended to H2 2022

Perspectives on Human Hearing Loss, Cochlear Regeneration, and the Potential for Hearing Restoration Therapies

CATEGORY:
Research

TITLE:
Perspectives on Human Hearing Loss, Cochlear Regeneration, and the Potential for Hearing Restoration Therapies

DESCRIPTION:
Most adults who acquire hearing loss find it to be a disability that is poorly corrected by current prosthetics. This gap drives current research in cochlear mechanosensory hair cell regeneration and in hearing restoration. Birds and fish can spontaneously regenerate lost hair cells through a process that has become better defined in the last few years. Findings from these studies have informed new research on hair cell regeneration in the mammalian cochlea. Hair cell regeneration is one part of…

CONTENT:
Brain Sci. 2020 Oct 20;10(10):E756. doi: 10.3390/brainsci10100756.

ABSTRACT

Most adults who acquire hearing loss find it to be a disability that is poorly corrected by current prosthetics. This gap drives current research in cochlear mechanosensory hair cell regeneration and in hearing restoration. Birds and fish can spontaneously regenerate lost hair cells through a process that has become better defined in the last few years. Findings from these studies have informed new research on hair cell regeneration in the mammalian cochlea. Hair cell regeneration is one part of the greater problem of hearing restoration, as hearing loss can stem from a myriad of causes. This review discusses these issues and recent findings, and places them in the greater social context of need and community.

PMID:33092183 | DOI:10.3390/brainsci10100756

SOURCE:
Brain sciences

DATE – PUBLISHED:
20 Oct 2020

DATE – ADDED:
Fri, 23 Oct 2020 06:00:00 -0400

DATE – FOUND:
10/23/20 07:18AM

PUBMED ID:
pubmed:33092183

DOI:
10.3390/brainsci10100756

PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33092183/

DOI LINK:
https://doi.org/10.3390/brainsci10100756

PUBLISHER LINK:
https://www.mdpi.com/2076-3425/10/10/756

Progenitor cell therapy for acquired pediatric nervous system injury: Traumatic brain injury and acquired sensorineural hearing loss

CATEGORY:
Research

TITLE:
Progenitor cell therapy for acquired pediatric nervous system injury: Traumatic brain injury and acquired sensorineural hearing loss

DESCRIPTION:
While cell therapies hold remarkable promise for replacing injured cells and repairing damaged tissues, cell replacement is not the only means by which these therapies can achieve therapeutic effect. For example, recent publications show that treatment with varieties of adult, multipotent stem cells can improve outcomes in patients with neurological conditions such as traumatic brain injury and hearing loss without directly replacing damaged or lost cells. As the immune system plays a central…

CONTENT:
Stem Cells Transl Med. 2020 Oct 9. doi: 10.1002/sctm.20-0026. Online ahead of print.

ABSTRACT

While cell therapies hold remarkable promise for replacing injured cells and repairing damaged tissues, cell replacement is not the only means by which these therapies can achieve therapeutic effect. For example, recent publications show that treatment with varieties of adult, multipotent stem cells can improve outcomes in patients with neurological conditions such as traumatic brain injury and hearing loss without directly replacing damaged or lost cells. As the immune system plays a central role in injury response and tissue repair, we here suggest that multipotent stem cell therapies achieve therapeutic effect by altering the immune response to injury, thereby limiting damage due to inflammation and possibly promoting repair. These findings argue for a broader understanding of the mechanisms by which cell therapies can benefit patients.

PMID:33034162 | DOI:10.1002/sctm.20-0026

SOURCE:
Stem cells translational medicine

DATE – PUBLISHED:
9 Oct 2020

DATE – ADDED:
Fri, 09 Oct 2020 06:00:00 -0400

DATE – FOUND:
10/09/20 07:09AM

PUBMED ID:
pubmed:33034162

DOI:
10.1002/sctm.20-0026

PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33034162/

DOI LINK:
https://doi.org/10.1002/sctm.20-0026

PUBLISHER LINK:
https://onlinelibrary.wiley.com/doi/10.1002/sctm.20-0026

Estimated FX-322 Phase 2a Study Completion Date: May 21, 2021

Very quick update:

The FX-322 Phase 2a clinical trial is now *officially* active and we now have an updated estimated completion date for the study: May 21, 2021.

Details below:

  • The FX-322 study record was updated on October 8, 2020
  • The study status was changed from “Recruiting” to “Active, not recruiting”
  • The study completion date was changed from September 30, 2020 [Anticipated] to May 21, 2021 [Anticipated].

FX-322 trial update October 8, 2020 now active

Source: History of Changes for Study: NCT04120116 (FX-322 in Adults With Stable Sensorineural Hearing Loss)

That’s all for now.

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