https://www.nature.com/articles/s41598-020-79946-z
Steady streaming as a method for drug delivery to the inner ear
Repurposed drug (dabrafenib) can treat hearing loss in humans
https://www.news-medical.net/news/20210107/Repurposed-drug-can-treat-hearing-loss-in-humans.aspx
Repurposed drug can treat hearing loss in humans
Glucose Protects Cochlear Hair Cells Against Oxidative Stress and Attenuates Noise-Induced Hearing Loss in Mice
CATEGORY:
Research
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:
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.
Zebrafish as a Biomedical Model for Stem Cells Research in Hearing Impairment [Preprint]
https://www.preprints.org/manuscript/202101.0099/v1
Zebrafish as a Biomedical Model for Stem Cells Research in Hearing Impairment
Salma Hafeez * ORCID logo
Version 1 : Received: 4 January 2021 / Approved: 5 January 2021 / Online: 5 January 2021 (14:23:23 CET)
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:
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.
Directed differentiation and direct reprogramming: Applying stem cell technologies to hearing research
https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.3315
Directed differentiation and direct reprogramming: Applying stem cell technologies to hearing research
Marta Roccio
First published: 30 December 2020 https://doi.org/10.1002/stem.3315
Funding information: Schmieder Bohrisch Foundation; Zürcher Stiftung für das Hören
Trk agonist drugs rescue noise-induced hidden hearing loss
CATEGORY:
Research
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.
Regulator of G Protein Signalling 4 (RGS4) as a Novel Target for the Treatment of Sensorineural Hearing Loss
https://www.mdpi.com/1422-0067/22/1/3/htm
Regulator of G Protein Signalling 4 (RGS4) as a Novel Target for the Treatment of Sensorineural Hearing Loss
This research represents a novel paradigm for the treatment of various forms of SNHL based on regulation of GPCR.
Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo
CATEGORY:
Research
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.
Presentation: OTO-413 Phase 1/2 Top-Line Results [PDF]
https://investors.otonomy.com/static-files/b9c45563-9e81-423d-8eb9-c12f103c56ac
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:
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
Building inner ears: recent advances and future challenges for in vitro organoid systems
https://www.nature.com/articles/s41418-020-00678-8
Building inner ears: recent advances and future challenges for in vitro organoid systems
Wouter H. van der Valk, Matthew R. Steinhart, Jingyuan Zhang & Karl R. Koehler
Cell Death & Differentiation volume 28, pages24–34(2021)Cite this article
Efferent control of hearing sensitivity and protection via inner ear supporting cells [Preprint]
https://www.biorxiv.org/content/10.1101/2020.12.03.409946v1
https://www.biorxiv.org/content/10.1101/2020.12.03.409946v1.full.pdf
Efferent control of hearing sensitivity and protection via inner ear supporting cells
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:
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:
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:
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.
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
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.
Promising targets for deafness drug discovery
Promising targets for deafness drug 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
Fast recovery of disrupted tip links induced by mechanical displacement of hair bundles
https://www.pnas.org/content/early/2020/11/13/2016858117
Proc Natl Acad Sci U S A
2020 Nov 16;202016858. doi: 10.1073/pnas.2016858117. Online ahead of print.
Fast recovery of disrupted tip links induced by mechanical displacement of hair bundles
Study of FX-322 in Patients with Severe SNHL to Start Before Year End
https://investors.frequencytx.com/news-releases/news-release-details/frequency-therapeutics-provides-business-updates-and-reports-3
Phase 1b Study in Patients with Severe SNHL to Start Before Year End
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:
If you want ALL of the FX-322 updates and exclusive hearing loss treatment-updates sign up for the free email newsletter.
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
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
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
Decibel Therapeutics Announces Exclusive Licensing Agreements for Hearing Loss Gene Therapy Technology
https://www.biospace.com/article/releases/decibel-therapeutics-announces-exclusive-licensing-agreements-for-hearing-loss-gene-therapy-technology/
Decibel Therapeutics Announces Exclusive Licensing Agreements for Hearing Loss Gene Therapy Technology
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/
Adenosine A2B receptor: A pathogenic factor and a therapeutic target for sensorineural hearing loss
https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202000939R
https://pubmed.ncbi.nlm.nih.gov/33131093/
Adenosine A2B receptor: A pathogenic factor and a therapeutic target for sensorineural hearing loss
Jeanne M. Manalo Hong Liu Dalian Ding John Hicks Hong Sun Richard Salvi Rodney E. Kellems Fred A. Pereira Yang Xia
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:
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:
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
Efficacy of SENS 401 in Subjects With Severe or Profound Sudden Sensorineural Hearing Loss
CATEGORY:
Clinical Trials
TITLE:
Efficacy of SENS 401 in Subjects With Severe or Profound Sudden Sensorineural Hearing Loss
INTERVENTION/TREATMENT:
PHASE:
DESCRIPTION:
Condition : Severe Sudden Sensorineural Hearing Loss
Interventions : Drug: SENS-401; Other: Placebo Oral Tablet
Sponsor : Sensorion
Recruiting
ID:
NCT03603314
STATUS:
DATE – FIRST POSTED:
Fri, 27 Jul 2018 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/NCT03603314
LINK – STUDY RECORD:
https://clinicaltrials.gov/ct2/show/NCT03603314
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].
Source: History of Changes for Study: NCT04120116 (FX-322 in Adults With Stable Sensorineural Hearing Loss)
That’s all for now.
For the latest FX-322 updates and news of other hearing loss treatments, sign up for the free once-weekly email newsletter.
Email michael@urgentresearch.com and say hello. Let me know what type of hearing loss treatment updates you like best. Feedback encouraged.
Also, remember to check out TinnitusTreatmentReport.com if you don’t already know about it.
FX-322 in Adults With Stable Sensorineural Hearing Loss
New item in Clinical Trial category found.
TITLE:
FX-322 in Adults With Stable Sensorineural Hearing Loss
DESCRIPTION:
Conditions : Sensorineural Hearing Loss; Noise Induced Hearing Loss; Sudden Sensorineural Hearing Loss
Interventions : Drug: FX-322; Drug: Placebo
Sponsor : Frequency Therapeutics
Active, not recruiting
ID:
NCT04120116
FIRST POSTED:
Wed, 09 Oct 2019 12:00:00 EDT
LAST UPDATE POSTED:
10/08/20 07:05AM
RECRUITMENT STATUS:
recruiting
INTERVENTION/DRUG:
FX-322
SOURCE LINK:
https://clinicaltrials.gov/ct2/show/NCT04120116?type=Intr&cond=Sensorineural+Hearing+Loss&phase=0124&lupd_s=10%2F07%2F2020&lupd_d=1&sort=nwst
LINK:
https://clinicaltrials.gov/ct2/show/NCT04120116
Inhibition of SRp30c may act as a new treatment way of glucocorticoid-resistant sudden sensorineural hearing loss
CATEGORY:
Research
TITLE:
GRβ Regulates Glucocorticoid Resistance in Sudden Sensorineural Hearing Loss
DESCRIPTION:
CONCLUSION: We clarified the mechanisms of high expression of GRβ in glucocorticoid-resistant sudden sensorineural hearing loss, and proved that the inhibition of SRp30c may act as a new treatment way of glucocorticoid-resistant sudden sensorineural hearing loss.
CONTENT:
Curr Pharm Biotechnol. 2020 Oct 8. doi: 10.2174/1389201021666201008163534. Online ahead of print.
ABSTRACT
BACKGROUND: In recent years, the incidence of sudden deafness has gradually increased, with a very limited understanding of the etiology and the pathogenesis. Glucocorticoids are the first choice for the treatment, but some hormoneresistant patients are not sensitive to glucocorticoid therapy. The pathogenesis is not yet known. In this study, we aim to construct HEI-OC1 cell line stably overexpressing glucocorticoid receptor beta (GRβ), and identify its exact role in the cases of glucocorticoid-resistant sudden deafness.
METHOD: We used the endotoxin lipopolysaccharide-stimulated cochlear hair cells (HEI-OC1) to investigate the relationship of inflammation factor IL-2, TNF alpha, and SRp30c with the high expression GRβ. We build a stable GRβ high expression HEI-OC1 cell line and clarified its effects on the therapeutic effect from Dexamethasone. MTT assay, colony formation assay, CCK-8 assay, Western blot, and RT-qPCR were utilized for the characterizations.
RESULTS: Dexamethasone reduced LPS-induced inflammatory response in HEI-OC1 cells (p<0.05), detected by MTT assay. Dexamethasone could protect HEI-OC1 cells, but its protective effect was weakened due to the transfection of SRp30c overexpression plasmid (p<0.05). The transfection of SRp30c over-expression plasmid in HEI-OC1 cells could elevate the expressions of GRβ (p<0.05). CONCLUSION: We clarified the mechanisms of high expression of GRβ in glucocorticoid-resistant sudden sensorineural hearing loss, and proved that the inhibition of SRp30c may act as a new treatment way of glucocorticoid-resistant sudden sensorineural hearing loss. PMID:33032506 | DOI:10.2174/1389201021666201008163534 SOURCE: Current pharmaceutical biotechnology DATE - PUBLISHED: 8 Oct 2020 DATE - ADDED: Fri, 09 Oct 2020 06:00:00 -0400 DATE - FOUND: 10/09/20 07:09AM PUBMED ID: pubmed:33032506 DOI: 10.2174/1389201021666201008163534 PUBMED LINK: https://pubmed.ncbi.nlm.nih.gov/33032506/ DOI LINK: https://doi.org/10.2174/1389201021666201008163534 PUBLISHER LINK: https://www.eurekaselect.com/186752/article
Altered outer hair cell mitochondrial and subsurface cisternae connectomics are candidate mechanisms for hearing-loss in mice
CATEGORY:
Research
TITLE:
Altered outer hair cell mitochondrial and subsurface cisternae connectomics are candidate mechanisms for hearing-loss in mice
DESCRIPTION:
Organelle crosstalk is vital for cellular functions. The propinquity of mitochondria, endoplasmic reticulum (ER), and plasma membrane promote regulation of multiple functions, which include intracellular Ca^(2+) flux, and cellular biogenesis. Although the purposes of apposing mitochondria and ER have been described, an understanding of altered organelle connectomics related to disease states is emerging. Since inner ear outer hair cell (OHC) degeneration is a common trait of age-related hearing…
CONTENT:
J Neurosci. 2020 Oct 5:JN-RM-2901-19. doi: 10.1523/JNEUROSCI.2901-19.2020. Online ahead of print.
ABSTRACT
Organelle crosstalk is vital for cellular functions. The propinquity of mitochondria, endoplasmic reticulum (ER), and plasma membrane promote regulation of multiple functions, which include intracellular Ca2+ flux, and cellular biogenesis. Although the purposes of apposing mitochondria and ER have been described, an understanding of altered organelle connectomics related to disease states is emerging. Since inner ear outer hair cell (OHC) degeneration is a common trait of age-related hearing loss, the objective of this study was to investigate whether the structural and functional coupling of mitochondria with subsurface cisternae (SSC), was affected by aging. We applied functional and structural probes to equal numbers of male and female mice with a hearing phenotype akin to human aging. We discovered the polarization of cristae and crista junctions in mitochondria tethered to the SSC in OHCs. Aging was associated with SSC stress and decoupling of mitochondria with the SSC, mitochondrial fission/fusion imbalance, a remarkable reduction in mitochondrial and cytoplasmic Ca2+ levels, reduced K+ -induced Ca2+ uptake, and marked plasticity of cristae membranes. A model of structure-based ATP production predicts profound energy stress in older OHCs. This report provides data suggesting that altered membrane organelle connectomics may result in progressive hearing loss.SIGNIFICANCE STATEMENT We address the question, “Do aged OHCs exhibit detectable changes in organelle connectomics that would help us better understand human hearing loss in a relevant mouse model?” Because of the close association of mitochondria SSC over much of the OHC inner surface, mitochondria-SSC connectomics appears to play a central role in hearing. In polarized cells such as OHCs, where there is functional segregation of apical versus basal regions, the relationship between altered organelle connectomics and hearing loss is unknown. We propose a mechanism of mitochondria-SSC dysregulation related to aging and OHC degeneration, showing distinct altered mitochondrial and cytoplasmic Ca2+ regulation, mitochondrial polarization, and fission/fusion imbalance, mitochondrial-SSC decoupling, and SSC and cellular energy stress.
PMID:33020216 | DOI:10.1523/JNEUROSCI.2901-19.2020
SOURCE:
The Journal of neuroscience : the official journal of the Society for Neuroscience
DATE – PUBLISHED:
5 Oct 2020
DATE – ADDED:
Tue, 06 Oct 2020 06:00:00 -0400
DATE – FOUND:
10/06/20 07:06AM
PUBMED ID:
pubmed:33020216
DOI:
10.1523/JNEUROSCI.2901-19.2020
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33020216/
DOI LINK:
https://doi.org/10.1523/JNEUROSCI.2901-19.2020
PUBLISHER LINK:
http://www.jneurosci.org/lookup/doi/10.1523/JNEUROSCI.2901-19.2020
Atomic-level maps of fine ear filaments shine a light on hearing loss
https://newatlas.com/medical/atomic-level-maps-fine-ear-filaments-hearing-loss/
Atomic-level maps of fine ear filaments shine a light on hearing loss
Biomarkers Suggesting Favorable Prognostic Outcomes in Sudden Sensorineural Hearing Loss
CATEGORY:
Research
TITLE:
Biomarkers Suggesting Favorable Prognostic Outcomes in Sudden Sensorineural Hearing Loss
DESCRIPTION:
Sudden sensorineural hearing loss (SSNHL) is a medical emergency, making detailed examination to determine possible causes and early treatment important. However, etiological examinations in SSNHL do not always reveal a cause, and several factors have been found to affect treatment outcomes. Various studies are being performed to determine the prognosis and effects of treatment in patients who experience sudden hearing loss, and to identify biomarkers associated with this condition. Embase,…
CONTENT:
Int J Mol Sci. 2020 Sep 30;21(19):E7248. doi: 10.3390/ijms21197248.
ABSTRACT
Sudden sensorineural hearing loss (SSNHL) is a medical emergency, making detailed examination to determine possible causes and early treatment important. However, etiological examinations in SSNHL do not always reveal a cause, and several factors have been found to affect treatment outcomes. Various studies are being performed to determine the prognosis and effects of treatment in patients who experience sudden hearing loss, and to identify biomarkers associated with this condition. Embase, PubMed, and the Cochrane database were searched using the key words SSNHL, prognostic, and biomarker. This search identified 4 articles in Embase, 28 articles in PubMed, and 36 in the Cochrane database. Of these 68 articles, 3 were duplicates and 37 were unrelated to the research topic. After excluding these articles, the remaining 28 articles were reviewed. Factors associated with SSNHL were divided into six categories: metabolic, hemostatic, inflammatory, immunologic, oxidative, and other factors. The associations between these factors with the occurrence of SSNHL and with patient prognosis were analyzed. Low monocyte counts, low neutrophil/lymphocyte ratio (NLR) and monocyte/high-density lipoproteins (HDL) cholesterol ratio (MHR), and low concentrations of fibrinogen, platelet glycoprotein (GP) IIIa, and TNF-α were found to be associated with good prognosis. However, these factors alone could not completely determine the onset of and recovery from SSNHL, suggesting the need for future basic and clinical studies.
PMID:33008090 | DOI:10.3390/ijms21197248
SOURCE:
International journal of molecular sciences
DATE – PUBLISHED:
30 Sep 2020
DATE – ADDED:
Sat, 03 Oct 2020 06:00:00 -0400
DATE – FOUND:
10/04/20 02:17AM
PUBMED ID:
pubmed:33008090
DOI:
10.3390/ijms21197248
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33008090/
DOI LINK:
https://doi.org/10.3390/ijms21197248
PUBLISHER LINK:
https://www.mdpi.com/1422-0067/21/19/7248
https://www.mdpi.com/1422-0067/21/19/7248/htm
Macrophages respond rapidly to ototoxic injury of lateral line hair cells but are not required for hair cell regeneration [Preprint]
https://www.biorxiv.org/content/10.1101/2020.09.28.314922v1.full
Macrophages respond rapidly to ototoxic injury of lateral line hair cells but are not required for hair cell regeneration
View ORCID ProfileMark E. Warchol, Angela Schrader, View ORCID ProfileLavinia Sheets
doi: https://doi.org/10.1101/2020.09.28.314922
Contrasting mechanisms for hidden hearing loss: synaptopathy vs myelin defects [Preprint]
https://www.biorxiv.org/content/10.1101/2020.10.04.324335v1.full
Contrasting mechanisms for hidden hearing loss: synaptopathy vs myelin defects
Maral Budak, Karl Grosh, View ORCID ProfileGabriel Corfas, Michal Zochowski, Victoria Booth
doi: https://doi.org/10.1101/2020.10.04.324335
How much will FX-322 cost? David Lucchino, Frequency Therapeutics CEO, talks pricing and value…
How much will FX-322 cost?
David Lucchino, CEO of Frequency Therapeutics, was recently asked for some “rough ideas around [the] pricing and reimbursement” of FX-322.
Here is a lightly edited* almost-word-for-word transcript of David’s response**:
*EDITED HOW? Disconnected parts of speech and filler words such as umm, well, you know, etc., have been removed for sake of clarity.
**SPOILER ALERT: David, understandably, does NOT give us a specific number. He gives us the answer we all expected, that of a responsible CEO. As he says, “specifics around pricing and regulatory ‘really need to be managed and played out appropriately'” (in other words, NOT eagerly telling us “FX-322 WILL COST EXACTLY THESE MANY DOLLARS” while the drug is still in phase 2a clinical trials).
Alas.
Specifics? Best I can do is this:
HOST: […] walk us through your thinking around the target patient population and maybe some kind of rough ideas around pricing and reimbursement […]
DAVID LUCCHINO: I’m still evolving our understanding of this as we really work in partner with the FDA to understand exactly the true, we think, impact of our therapy. So it’s hard for me to speak in any absolutes. We know that the market is absolutely substantial and the unmet clinical need is very, very high. We think that hearing aids will continue to have a real role and be a good option for patients, though we think having a therapy that can truly start to heal someone’s hearing and create a healthy cochlea, if you will, is going to be a very strong value proposition both with or without hearing aids. I think that specifics around pricing and regulatory, those really need to be managed and played out appropriately. I think that we’re aware of what hearing aids are priced at, and we’re aware of what cochlear implants are priced at, and how hearing aids are handled from a regulatory standpoint and our goal is to deliver a highly effective therapy and do it in a way where we can continue to build out a very successful company that investors will recognize for years and years to come.
HOST: Excellent, super helpful.
SOURCE: Where is this from? These comments were made during a live Q&A at the Oppenheimer Virtual Fall Healthcare Life Sciences & MedTech Summit, which took place on Tuesday, September 22, 2020 at 10:00 am Eastern Time.
As David’s comments suggest, a lot of work goes into determining the price of a treatment such as FX-322. Meanwhile, the drug only recently completed enrollment for its Phase 2a study.
So don’t expect any “Hey it will cost THIS many dollars” answers yet…
For now, this recent commentary is the most recent and up-to-date information regarding FX-322’s price tag. Straight from the CEO’s mouth.
And let’s be honest, it is the reply we all expected… But with some interesting “price anchoring” thrown in with the mention of hearing aid costs (average price: $2372) and cochlear implant costs (average price: between $30,000-$100,000).***
Why would David mention those price points? How do drug companies calculate price? How do comparisons and price anchoring factor into that calculation?
Hmmmm…
Let the speculation begin!
LINK TO VIDEO: If you want to watch the interview, here is a link to the video recording of the Frequency Therapeutics virtual event webcast (the FX-322 pricing-related comments begin at around 39:00):
https://wsw.com/webcast/oppenheimer5/freq/2713518
And…
If you want an easy way to follow FX-322 including any future updates RE: cost of FX-322, join the weekly email update list. It’s a free, once-weekly email [starting soon] that lists all the new links that were added to this site’s front page during the previous 7 days. No spam, no nonsense.
***Reference: https://www.hearingtracker.com/how-much-do-hearing-aids-cost, https://www.hearingtracker.com/cochlear-implants#a-how-much-do-cochlear-implants-cost.
Decades-old theory on how ears work is wrong: After 30 years, scientists still don’t know how the ear tells the brain what it is hearing
https://massivesci.com/notes/ear-hair-hearing-sound/
Decades-old theory on how ears work is wrong
After 30 years, scientists still don’t know how the ear tells the brain what it is hearing
Frequency Therapeutics Completes Enrollment of FX-322 Phase 2a Study for Sensorineural Hearing Loss
https://investors.frequencytx.com/news-releases/news-release-details/frequency-therapeutics-completes-enrollment-fx-322-phase-2a
Frequency Therapeutics Completes Enrollment of FX-322 Phase 2a Study for Sensorineural Hearing Loss
Altered Brain Activity and Functional Connectivity in Sudden Sensorineural Hearing Loss
CATEGORY:
Research
TITLE:
Altered Brain Activity and Functional Connectivity in Unilateral Sudden Sensorineural Hearing Loss
DESCRIPTION:
CONCLUSION: SSNHL causes functional alterations in brain regions, mainly in the striatum, auditory cortex, visual cortex, MTG, AG, precuneus, and limbic lobes within the acute period of hearing loss.
CONTENT:
Neural Plast. 2020 Sep 22;2020:9460364. doi: 10.1155/2020/9460364. eCollection 2020.
ABSTRACT
BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is an otologic emergency and could lead to social difficulties and mental disorders in some patients. Although many studies have analyzed altered brain function in populations with hearing loss, little information is available about patients with idiopathic SSNHL. This study is aimed at investigating brain functional changes in SSNHL via functional magnetic resonance imaging (fMRI).
METHODS: Thirty-six patients with SSNHL and thirty well-matched normal hearing individuals underwent resting-state fMRI. Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and functional connectivity (FC) values were calculated.
RESULTS: In the SSNHL patients, ALFF and fALFF were significantly increased in the bilateral putamen but decreased in the right calcarine cortex, right middle temporal gyrus (MTG), and right precentral gyrus. Widespread increases in FC were observed between brain regions, mainly including the bilateral auditory cortex, bilateral visual cortex, left striatum, left angular gyrus (AG), bilateral precuneus, and bilateral limbic lobes in patients with SSNHL. No decreased FC was observed.
CONCLUSION: SSNHL causes functional alterations in brain regions, mainly in the striatum, auditory cortex, visual cortex, MTG, AG, precuneus, and limbic lobes within the acute period of hearing loss.
PMID:33029130 | PMC:PMC7527900 | DOI:10.1155/2020/9460364
SOURCE:
Neural plasticity
DATE – PUBLISHED:
22 Sep 2020
DATE – ADDED:
Thu, 08 Oct 2020 06:00:00 -0400
DATE – FOUND:
10/08/20 06:42AM
PUBMED ID:
pubmed:33029130
DOI:
10.1155/2020/9460364
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33029130/
DOI LINK:
https://doi.org/10.1155/2020/9460364
PUBLISHER LINK:
https://www.hindawi.com/journals/np/2020/9460364/
SCN11A Gene Deletion Causes Sensorineural Hearing Loss by Impairing the Ribbon Synapses and Auditory Nerves [Preprint]
https://www.researchsquare.com/article/rs-46143/v1
SCN11A Gene Deletion Causes Sensorineural Hearing Loss by Impairing the Ribbon Synapses and Auditory Nerves
Mian Zu, Wei-wei Guo, Tao Cong, Fei Ji, Shi-li Zhang, Yue Zhang, Xin Song, Wei Sun, David Z.Z. He, Wei-guo Shi, Shiming Yang
DOI:
10.21203/rs.3.rs-46143/v1
Hearing Loss – Reddit
https://www.reddit.com/r/HearingLoss/
Hearing Loss – Reddit
r/HearingLoss
Frequency’s hearing loss treatment shows long-term promise
https://www.fiercebiotech.com/biotech/frequency-s-hearing-loss-treatment-shows-long-term-promise
OTO-413 in Subjects With Speech-in-Noise Hearing Impairment
https://clinicaltrials.gov/ct2/show/NCT04129775?type=Intr&cond=Hearing+Loss&lupd_s=10%2F03%2F2019&lupd_d=14&sort=nwst
Condition : Sensorineural Hearing Loss
Interventions : Drug: OTO-413; Drug: Placebo
Sponsor : Otonomy, Inc.
Recruiting
OTO-413 in Subjects With Speech-in-Noise Hearing Impairment
NCT04129775
Thu, 17 Oct 2019 12:00:00 EDT
Last Update Posted: 10/17/19 08:21AM
https://clinicaltrials.gov/ct2/show/NCT04129775
OTO-413 in Subjects With Speech-in-Noise Hearing Impairment
Updated: September 14, 2020
Active, not recruiting
Study Type : Interventional (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Phase 1/2 Study of OTO-413 Given as a Single Intratympanic Injection in Subjects With Speech-in-noise Hearing Impairment
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020
Frequency Therapeutics Presents Results Demonstrating Sustained Improvement in Hearing Loss Patients Treated with FX-322
https://investors.frequencytx.com/news-releases/news-release-details/frequency-therapeutics-presents-results-demonstrating-sustained
Frequency Therapeutics Presents Results Demonstrating Sustained Improvement in Hearing Loss Patients Treated with FX-322
Evidence of Durable Hearing Improvements in Follow-Up with Patients from Phase 1/2 Study; Speech Intelligibility and Audibility Sustained for Up to 21 Months After Initial Dosing
Data Highlighted at the 2020 American Academy of Otolaryngology – Head and Neck Surgery (AAO-HNS) Annual Meeting
Role of protein in development of new hearing hair cells: Finding could lead to future treatments for hearing loss
https://www.sciencedaily.com/releases/2020/09/200911200012.htm
Role of protein in development of new hearing hair cells
Finding could lead to future treatments for hearing loss
Date:
September 11, 2020
Source:
University of Maryland School of Medicine
Summary:
Researchers have conducted a study that has determined the role that a critical protein plays in the development of hair cells. These hair cells are vital for hearing. Some of these cells amplify sounds that come into the ear, and others transform sound waves into electrical signals that travel to the brain.
Effects of Growth Factors and the MicroRNA-183 Family on Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells Towards Auditory Neuron-Like Cells
https://www.dovepress.com/effects-of-growth-factors-and-the-microrna-183-family-on-differentiati-peer-reviewed-fulltext-article-SCCAA
https://doi.org/10.2147/SCCAA.S248526
Effects of Growth Factors and the MicroRNA-183 Family on Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells Towards Auditory Neuron-Like Cells
Authors Farnoosh G, Mahmoudian-Sani MR
Published 10 September 2020 Volume 2020:13 Pages 79—89
DOI https://doi.org/10.2147/SCCAA.S248526
Bromodomain Protein BRD4 Is Essential for Hair Cell Function and Survival
https://www.frontiersin.org/articles/10.3389/fcell.2020.576654/full
ORIGINAL RESEARCH ARTICLE
Front. Cell Dev. Biol., 08 September 2020 | https://doi.org/10.3389/fcell.2020.576654
Bromodomain Protein BRD4 Is Essential for Hair Cell Function and Survival
Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers
https://link.springer.com/article/10.1007/s12035-020-02092-0
Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers
Decibel Therapeutics to Present at Citi’s 15th Annual BioPharma Virtual Conference on September 8, 2020
Decibel Therapeutics to Present at Citi’s 15th Annual BioPharma Virtual Conference
https://www.businesswire.com/news/home/20200902005279/en/Decibel-Therapeutics-Present-Citis-15th-Annual-BioPharma
Decibel Therapeutics to Present at Citi’s 15th Annual BioPharma Virtual Conference
Circulating microRNAs as potentially new diagnostic biomarkers of idiopathic sudden sensorineural hearing loss
https://www.tandfonline.com/doi/abs/10.1080/00016489.2020.1810859?journalCode=ioto20
https://www.ncbi.nlm.nih.gov/pubmed/32876518?dopt=Abstract
Related Articles
Circulating microRNAs as potentially new diagnostic biomarkers of idiopathic sudden sensorineural hearing loss.
Acta Otolaryngol. 2020 Sep 02;:1-8
Authors: Ha SM, Hwang KR, Park IH, Park S, Choi JS, Park DJ, Park JE, Lee SH, Lee HY, Seo YJ
Abstract
BACKGROUND: Early detection of inner ear cell damage can reduce the chances of permanent damage to hearing ability. However, current inner ear cell damage detection methods can detect damage only after the patient has lost hearing ability. MicroRNA expression levels in circulating systems are affected in diseases or conditions arising from the distant lesions. Therefore, detection of circulating microRNA expression levels could be one of the best ways to obtain information on inaccessible lesion sites.
AIMS/OBJECTIVES: This study aims to establish a method for monitoring idiopathic sudden sensorineural hearing loss (ISSNHL) by analyzing circulating microRNA expression levels. 21 ISSNHL patients and 24 healthy controls were enrolled.
MATERIAL AND METHODS: Real-time quantitative polymerase chain reaction was performed for detecting expression levels of circulating microRNAs.
RESULTS: Among eight circulating microRNAs, expression levels of five circulating microRNAs significantly differed between ISSNHL patients and healthy controls. circulating microRNA expression levels correlates with treatment outcomes and hearing ability.
CONCLUSIONS AND SIGNIFICANCE: Using methods combining the evaluation of miR-183, miR-210, miR-18b, and miR-23a cut-off values identified in ISSNHL patients and healthy controls during receiver operating characteristic curve analysis, sensitivity and specificity of 80.95% (17/21) and 87.50% (21/24) were obtained, respectively.
PMID: 32876518 [PubMed – as supplied by publisher]
Dextromethorphan Attenuates Sensorineural Hearing Loss in an Animal Model and Population-Based Cohort Study
https://www.mdpi.com/1660-4601/17/17/6336/htm
https://pubmed.ncbi.nlm.nih.gov/32878128/
Open Access
Article
Dextromethorphan Attenuates Sensorineural Hearing Loss in an Animal Model and Population-Based Cohort Study
Int. J. Environ. Res. Public Health 2020, 17(17), 6336; https://doi.org/10.3390/ijerph17176336
Received: 31 July 2020 / Revised: 27 August 2020 / Accepted: 28 August 2020 / Published: 31 August 2020
COMMENT: This link was added manually from a PubMed search (September 9, 2020), it has not (yet?) been retrieved by the system. Add this potentially missed link to error logbook, investigate cause.
The Role of Anti-Endothelial Cell Autoantibodies and Immune Response in Acute Low-Tone Hearing Loss
https://journals.sagepub.com/doi/10.1177/0145561320952501
https://www.ncbi.nlm.nih.gov/pubmed/32865463?dopt=Abstract
Related Articles
The Role of Anti-Endothelial Cell Autoantibodies and Immune Response in Acute Low-Tone Hearing Loss.
Ear Nose Throat J. 2020 Aug 31;:145561320952501
Authors: Chen D, Wang Z, Jia G, Mao H, Ni Y
Abstract
OBJECTIVE: Immunity is associated with acute low tone hearing loss. However, the exact pathophysiology of immunity-mediated acute low tone hearing loss remains unknown. In this study, we evaluated the presence, therapeutic effectiveness, and immunopathological mechanisms of anti-endothelial cell autoantibodies (AECEs) in patients with acute low-frequency hearing loss.
MATERIAL AND METHODS: Forty-nine patients who were treated as inpatients having acute low-frequency hearing loss and additional symptoms, such as ear fullness, tinnitus, dizziness, or hyperacusis, were enrolled in this study. Serum samples from these patients were collected for laboratory serum autoimmunity detection, including AECAs, antinuclear antibodies, immunoglobulin, and circular immune complex. Therapeutic responses to combination therapy in short-term outcome and serum cytokine levels were compared between AECA-positive and AECA-negative patients.
RESULTS: Anti-endothelial cell autoantibodies-positive patients tended to show significantly less response to standard therapy compared with AECAs controls (P < .05). Moreover, some serum cytokine levels elevated in both AECAs- and AECAs+ groups. Positive ratio of interleukin-8 and concentrations of macrophage inflammatory protein-1α were found higher in AECAs+ groups (P < .05). CONCLUSION: The results supported that AECAs might wield influence on the short-term outcome of acute low-tone hearing loss (ALHL) treatment. Furthermore, AECA-mediated acute low-frequency hearing loss possibly involved dysregulation of inflammation process and release of cytokines. PMID: 32865463 [PubMed - as supplied by publisher]
Protective Effects of EPI-743 on Noise-Induced Hearing Loss [Completed]
https://clinicaltrials.gov/ct2/show/NCT02257983?type=Intr&cond=Hearing+Loss&lupd_s=08%2F17%2F2020&lupd_d=14&sort=nwst
Condition : Noise-induced Hearing Loss
Interventions : Drug: EPI-743; Drug: Placebo
Sponsor : PTC Therapeutics
Completed
Protective Effects of EPI-743 on Noise-Induced Hearing Loss
NCT02257983
Tue, 07 Oct 2014 12:00:00 EDT
Last Update Posted: 08/31/20 07:19AM
Loss of RAD6B induces degeneration of the cochlea in mice
https://www.sciencedirect.com/science/article/abs/pii/S0006291X2031562X?via%3Dihub
https://pubmed.ncbi.nlm.nih.gov/32868078/
Loss of RAD6B induces degeneration of the cochlea in mice
Yangping Ma 1, Yanfeng Song 1, Rong Shen 1, Panpan Li 1, Han Ding 1, Zhao Guo 1, Xiangwen Liu 1, Degui Wang 2
Affiliations expand
PMID: 32868078 DOI: 10.1016/j.bbrc.2020.08.017
Abstract
Presbycusis is a form of age-related hearing loss (AHL). Many studies have shown that the degeneration of various structures in the cochlea of the inner ear is related to AHL, and DNA damage is an important factor leading to the above process. As an E2 ubiquitin-conjugated enzyme, RAD6B plays an important role in DNA damage repair (DDR) through histone ubiquitination. However, the molecular mechanism is still unclear. In this study, we investigated the role of RAD6B in the morphological changes and DDR mechanisms in aging-related degeneration of the cochlea of mice. We observed that the hair cells, stria vascularis and spiral ganglion in the cochlea of the RAD6B knockout mice showed significant degenerative changes and abnormal expression of proteins associated with DDR mechanisms compared with those of the littermate wild-type mice. In conclusion, our results suggest that the deletion of RAD6B may lead to abnormalities in DDR, thereby accelerating the degeneration of various structures in the cochlea and senescence and apoptosis of cochlea cells.
Keywords: Cochlea; DNA damage; Degeneration; RAD6B; Ubiquitin.
Systematic Transcriptome Analysis of Noise-Induced Hearing Loss Pathogenesis Suggests Inflammatory Activities and Multiple Susceptible Molecules and Pathways
CATEGORY:
Research
TITLE:
Systematic Transcriptome Analysis of Noise-Induced Hearing Loss Pathogenesis Suggests Inflammatory Activities and Multiple Susceptible Molecules and Pathways
DESCRIPTION:
Noise-induced hearing loss (NIHL) is characterized by damage to cochlear neurons and associated hair cells; however, a systematic evaluation of NIHL pathogenesis is still lacking. Here, we systematically evaluated differentially expressed genes of 22 cochlear samples in an NIHL mouse model. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and weighted gene co-expression network analysis (WGCNA). Core modules were detected using protein-protein interactions…
CONTENT:
Front Genet. 2020 Aug 28;11:968. doi: 10.3389/fgene.2020.00968. eCollection 2020.
ABSTRACT
Noise-induced hearing loss (NIHL) is characterized by damage to cochlear neurons and associated hair cells; however, a systematic evaluation of NIHL pathogenesis is still lacking. Here, we systematically evaluated differentially expressed genes of 22 cochlear samples in an NIHL mouse model. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and weighted gene co-expression network analysis (WGCNA). Core modules were detected using protein-protein interactions and WGCNA with functional annotation, diagnostic value evaluation, and experimental validation. Pooled functional annotation suggested the involvement of multiple inflammatory pathways, including the TNF signaling pathway, IL-17 signaling pathway, NF-kappa B signaling pathway, rheumatoid arthritis, and p53 signaling pathway. The core modules suggested that responses to cytokines, heat, cAMP, ATP, mechanical stimuli, and immune responses were important in NIHL pathogenesis. These activities primarily occurred on the external side of the plasma membrane, the extracellular region, and the nucleus. Binding activities, including CCR2 receptor binding, protein binding, and transcription factor binding, may be important. Additionally, the hub molecules with diagnostic value included Relb, Hspa1b, Ccl2, Ptgs2, Ldlr, Plat, and Ccl17. An evaluation of Relb and Hspa1b protein levels showed that Relb was upregulated in spiral ganglion neurons, which might have diagnostic value. In conclusion, this study indicates that the inflammatory response is involved in auditory organ changes in NIHL pathogenesis; moreover, several molecules and activities have essential and subtle influences that have translational potential for pharmacological intervention.
PMID:33005175 | PMC:PMC7483666 | DOI:10.3389/fgene.2020.00968
SOURCE:
Frontiers in genetics
DATE – PUBLISHED:
28 Aug 2020
DATE – ADDED:
Fri, 02 Oct 2020 06:00:00 -0400
DATE – FOUND:
10/02/20 07:34AM
PUBMED ID:
pubmed:33005175
DOI:
10.3389/fgene.2020.00968
PUBMED LINK:
https://pubmed.ncbi.nlm.nih.gov/33005175/
DOI LINK:
https://doi.org/10.3389/fgene.2020.00968
PUBLISHER LINK:
https://www.frontiersin.org/article/10.3389/fgene.2020.00968/full
Drug development for noise-induced hearing loss
https://www.tandfonline.com/doi/abs/10.1080/17460441.2020.1806232?journalCode=iedc20
https://pubmed.ncbi.nlm.nih.gov/32838572/
Drug development for noise-induced hearing loss
Isabel Varela-Nieto ,Silvia Murillo-Cuesta,Miryam Calvino,Rafael Cediel &Luis Lassaletta
Received 23 Mar 2020, Accepted 03 Aug 2020, Published online: 25 Aug 2020
Download citation https://doi.org/10.1080/17460441.2020.1806232 CrossMark LogoCrossMark
Loud noise exposure differentially affects subpopulations of auditory cortex pyramidal cells [Preprint]
https://www.biorxiv.org/content/biorxiv/early/2020/08/31/2020.08.25.264200.full.pdf
Loud noise exposure differentially affects subpopulations of auditory cortex pyramidal cells
doi: https://doi.org/10.1101/2020.08.25.264200
LIN28B/let-7 control the ability of neonatal murine auditory supporting cells to generate hair cells through mTOR signaling
https://www.pnas.org/content/early/2020/08/20/2000417117
https://pubmed.ncbi.nlm.nih.gov/32826333/
RESEARCH ARTICLE
LIN28B/let-7 control the ability of neonatal murine auditory supporting cells to generate hair cells through mTOR signaling
Xiao-Jun Li and View ORCID ProfileAngelika Doetzlhofer
PNAS first published August 21, 2020 https://doi.org/10.1073/pnas.2000417117
Decades-old model of slow adaptation in sensory hair cells is not supported in mammals
https://advances.sciencemag.org/content/6/33/eabb4922
Decades-old model of slow adaptation in sensory hair cells is not supported in mammals
View ORCID ProfileGiusy A. Caprara1, View ORCID ProfileAndrew A. Mecca1,2 and View ORCID ProfileAnthony W. Peng1,*
See all authors and affiliations
Science Advances 14 Aug 2020:
Vol. 6, no. 33, eabb4922
DOI: 10.1126/sciadv.abb4922
Frequency Therapeutics Expects to Share FX-322 Phase 2a Study Results in Q2 2021
https://www.businesswire.com/news/home/20200812005136/en/
expects to achieve target enrollment by early in the fourth quarter of 2020. Based on this timeline, the Company expects to report study data in the second quarter of 2021.
Frequency Therapeutics Provides Business Updates and Reports Second Quarter 2020 Financial Results
Expects to Complete Enrollment of FX-322 Phase 2a Study for Sensorineural Hearing Loss by Early Q4 2020; Study Readout Anticipated in Q2 2021
Recently Announced Clinical Data Show FX-322 Delivery to the Cochlea and Preliminary Evidence of a Durable Clinical Benefit; Plans New Studies in Additional Patient Populations
Raised $42.3 Million Private Placement, Providing Company Runway into 2023
August 12, 2020 07:30 AM Eastern Daylight 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 business updates and financial results for the second quarter ended June 30, 2020.
“We are pleased with the steady progress in our Phase 2a study, despite the challenges of the pandemic, and we anticipate completing enrollment early in the fourth quarter of 2020 and sharing data from the study in the second quarter of 2021,” said Frequency Therapeutics Chief Executive Officer David L. Lucchino. “In the last quarter, we generated compelling cochlear drug delivery data for FX-322, as well as important durability data suggesting that some patients who were given a single injection of FX-322 in our original Phase 1/2 study maintained statistically significant improvements in word recognition between 12 and 21 months following administration. We believe that these clinical advances are important building blocks as we work to further our understanding of FX-322 drug activity and the patient populations we hope to treat.
Application of Mesenchymal Stem Cell Therapy and Inner Ear Regeneration for Hearing Loss: A Review
https://www.mdpi.com/1422-0067/21/16/5764/htm
https://www.ncbi.nlm.nih.gov/pubmed/32796705?dopt=Abstract
Application of Mesenchymal Stem Cell Therapy and Inner Ear Regeneration for Hearing Loss: A Review.
Int J Mol Sci. 2020 Aug 11;21(16):
Authors: Kanzaki S, Toyoda M, Umezawa A, Ogawa K
Abstract
Inner and middle ear disorders are the leading cause of hearing loss, and are said to be among the greatest risk factors of dementia. The use of regenerative medicine for the treatment of inner ear disorders may offer a potential alternative to cochlear implants for hearing recovery. In this paper, we reviewed recent research and clinical applications in middle and inner ear regeneration and cell therapy. Recently, the mechanism of inner ear regeneration has gradually been elucidated. “Inner ear stem cells,” which may be considered the precursors of various cells in the inner ear, have been discovered in the cochlea and vestibule. Research indicates that cells such as hair cells, neurons, and spiral ligaments may form promising targets for inner ear regenerative therapies by the transplantation of stem cells, including mesenchymal stem cells. In addition, it is necessary to develop tests for the clinical monitoring of cell transplantation. Real-time imaging techniques and hearing rehabilitation techniques are also being investigated, and cell therapy has found clinical application in cochlear implant techniques.
PMID: 32796705 [PubMed – as supplied by publisher]
Insulin-like growth factor 1 (IGF-1): role in the auditory system and therapeutic potential in otology
https://journals.lww.com/co-otolaryngology/Abstract/9000/Insulin_like_growth_factor_1__role_in_the_auditory.99119.aspx
https://www.ncbi.nlm.nih.gov/pubmed/32796270?dopt=Abstract
Insulin-like growth factor 1: role in the auditory system and therapeutic potential in otology.
Curr Opin Otolaryngol Head Neck Surg. 2020 Aug 10;:
Authors: Gao L, Nakagawa T
Abstract
PURPOSE OF REVIEW: Insulin-like growth factor 1 (IGF-1) is a hormone necessary for the development, growth, and maintenance of various organs, and has been used as a therapeutic agent in clinical settings. This review aimed to illustrate its role in the auditory systems and its potential use as a therapeutic in the field of otology.
RECENT FINDINGS: Previous animal studies have indicated the critical role of IGF-1 in the development and maintenance of the auditory system, especially in the cochlea. A clinical study demonstrated a close relationship between the serum level of IGF-1 and the progression of age-related hearing impairment, suggesting its importance in the maintenance of hearing in humans. More recently, its effect on the regeneration of cochlear synapses has been reported using explant cultures, which could explain the course of hearing recovery in patients who underwent topical IGF-1 application for the treatment of sudden sensorineural hearing loss.
SUMMARY: Recent advances in experimental and clinical investigations have revealed the importance of IGF-1 in the maintenance of the auditory function. On the basis of broad targets, its clinical application will expand to the field of otology in the future.
PMID: 32796270 [PubMed – as supplied by publisher]
Opposite Roles of NT-3 and BDNF in Synaptic Remodeling of the Inner Ear Induced by Electrical Stimulation
https://link.springer.com/article/10.1007%2Fs10571-020-00935-x
Published: 08 August 2020
Opposite Roles of NT-3 and BDNF in Synaptic Remodeling of the Inner Ear Induced by Electrical Stimulation
Qiang Li, Min Chen, Chen Zhang, Tianhao Lu, Shiyao Min & Shufeng Li
Cellular and Molecular Neurobiology (2020)Cite this article
65 Accesses
1 Altmetric
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Three-Dimensional Otic Neuronal Progenitor Spheroids Derived from Human Embryonic Stem Cells
https://www.liebertpub.com/doi/10.1089/ten.tea.2020.0078
Three-Dimensional Otic Neuronal Progenitor Spheroids Derived from Human Embryonic Stem Cells
Rachel A. Heuer, Kevin T. Nella, Hsiang-Tsun Chang, Kyle S. Coots, Andrew M. Oleksijew, Christian B. Roque, Luisa H.A. Silva, Tammy L. McGuire, Kazuaki Homma, and Akihiro J. Matsuoka
Published Online: 7 Aug 2020 https://doi.org/10.1089/ten.tea.2020.0078
P2rx3 regulates spiral ganglion neuron (SGN) branch refinement, promotes auditory neuron maturation, and could play a role in regenerating lost auditory connections in hearing loss
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418533/
https://www.eneuro.org/content/eneuro/7/4/ENEURO.0179-20.2020.full.pdf
The Purinergic Receptor P2rx3 is Required for Spiral Ganglion Neuron Branch Refinement during Development
Zhirong Wang, Johnny S. Jung, Talya C. Inbar, Katherine M. Rangoussis, Christian Faaborg-Andersen,
and Thomas M. Coate
https://doi.org/10.1523/ENEURO.0179-20.2020
Department of Biology, Georgetown University, Washington, DC 20007
P2rx3 receptors are a class of ionotropic purinergic receptors that are expressed in sensory afferent neurons and have been shown to play essential roles in sensory transduction. However, little is known about how P2rx3 functions in neuronal morphogenesis and synaptic connectivity. Here, we found that P2rx3 is expressed by spiral ganglion neurons (SGNs) and hair cells during cochlear development. Using P2rx3 null mice combined with genetic sparse labeling, we discovered P2rx3 regulates SGN branch refinement, which is a function of P2rx3 distinguishable from the more conventionally-known role in neural transduction. These results offer new insights into how P2rx3 promotes auditory neuron maturation, which may be useful for endeavors aimed at regenerating lost auditory connections in hearing loss.
Efficacy and Safety of AM-111 as Acute Sudden Sensorineural Hearing Loss Treatment [Terminated]
https://clinicaltrials.gov/ct2/show/NCT02809118?type=Intr&cond=Hearing+Loss&lupd_s=07%2F24%2F2020&lupd_d=14&sort=nwst
Condition : Hearing Loss, Idiopathic Sudden Sensorineural
Interventions : Drug: AM-111 0.4 mg/ml; Drug: AM-111 0.8 mg/ml; Other: Placebo
Sponsor : Auris Medical, Inc.
Terminated
Efficacy and Safety of AM-111 as Acute Sudden Sensorineural Hearing Loss Treatment
NCT02809118
Wed, 22 Jun 2016 12:00:00 EDT
Last Update Posted: 08/07/20 06:52AM
PIPE-505 Clinical Trial Update: Pipeline adds 4 new study locations across the United States…
As anticipated, Pipeline Therapeutics has added additional clinical trial sites to its phase 1/2a study of PIPE-505 for hearing loss.
The official study record (NCT04462198), updated on August 6, 2020, now includes five study locations across the U.S., four of which are now recruiting participants:
- Boca Raton, Florida, United States, 33487 – added July 17 – Recruiting
- Winston-Salem, North Carolina, United States, 27103 – added July 27 – Recruiting
- New Albany, Indiana, United States, 47150 – added August 1 – Recruiting
- Louisville, Kentucky, United States, 40220 – added August 1 – Recruiting
- Kansas City, Kansas, United States, 66160 – added August 4 – Not yet recruiting
This post will be updated to include any further changes to the study record. For email updates (which will be starting soon), join the announcement list while it is still open.
Otonomy Announces Exclusive License Agreement with Kyorin for Novel Compound in OTO-6XX Hearing Loss Program
https://www.globenewswire.com/news-release/2020/08/03/2071620/0/en/Otonomy-Announces-Exclusive-License-Agreement-with-Kyorin-for-Novel-Compound-in-OTO-6XX-Hearing-Loss-Program.html
Otonomy Announces Exclusive License Agreement with Kyorin for Novel Compound in OTO-6XX Hearing Loss Program
Compound has potential to benefit patients with severe hearing loss
Stem Cell-Based Therapeutic Approaches to Restore Sensorineural Hearing Loss in Mammals
https://www.hindawi.com/journals/np/2020/8829660/
Reestablishing Neural Plasticity in Regenerated Spiral Ganglion Neurons and Sensory Hair Cells for Hearing Loss 2020
View this Special Issue
Review Article | Open Access
Volume 2020 |Article ID 8829660 | 10 pages | https://doi.org/10.1155/2020/8829660
Stem Cell-Based Therapeutic Approaches to Restore Sensorineural Hearing Loss in Mammals
Recent Advancements in Understanding the Role of Epigenetics in the Auditory System
https://www.sciencedirect.com/science/article/abs/pii/S037811192030665X?via%3Dihub
Review Gene
2020 Jul 29;144996. doi: 10.1016/j.gene.2020.144996. Online ahead of print.
Recent Advancements in Understanding the Role of Epigenetics in the Auditory System
Rahul Mittal 1, Nicole Bencie 1, George Liu 1, Nicolas Eshraghi 1, Eric Nisenbaum 1, Susan H Blanton 2, Denise Yan 1, Jeenu Mittal 1, Christine T Dinh 1, Juan I Young 3, Feng Gong 4, Xue Zhong Liu 5
Affiliations expand
PMID: 32738421 DOI: 10.1016/j.gene.2020.144996
A metal-organic framework based inner ear delivery system for the treatment of noise-induced hearing loss
https://pubs.rsc.org/en/content/articlelanding/2020/NR/D0NR04860G#!divAbstract
https://www.ncbi.nlm.nih.gov/pubmed/32725028?dopt=Abstract
Related Articles
A metal-organic framework based inner ear delivery system for the treatment of noise-induced hearing loss.
Nanoscale. 2020 Jul 29;:
Authors: Xu X, Lin K, Wang Y, Xu K, Sun Y, Yang X, Yang M, He Z, Zhang Y, Zheng H, Chen X
Abstract
Noise-induced hearing loss (NIHL) is associated with both acute and chronic noise exposure. The application of steroid hormones is the first-line treatment for NIHL. However, a high dose of steroid hormone in the body is necessary to maintain its efficacy and causes side effects, such as headache and osteoporosis. In this work, we prepared a zeolitic imidazolate framework (ZIF)-based system for steroid hormone delivery in the inner ear. Methylprednisolone (MP), a typical steroid hormone, was encapsulated into ZIF-90 nanoparticles (NPs) using one-pot synthesis method. The obtained MP@ZIF-90 NPs are negatively charged and 120 nm in size and showed good biocompatibility and stability at a pH value of 7.4. After intraperitoneal injection, ZIF-90 could efficiently protect drugs during peripheral blood circulation, enter the inner ear via the blood labyrinthine barrier (BLB) and slowly release the drugs. Auditory brainstem response (ABR) tests indicated that MP@ZIF-90 exhibits better protection of mice from noise than those using the free MP and ZIF-8 with encapsulated MP (MP@ZIF-8). More importantly, MP@ZIF-90 showed no defects to the inner ear after being treated for noise and low nephrotoxicity during therapy, which demonstrates the biocompatibility of this material. We believe the ZIF-90 based delivery system is an efficient strategy for inner ear therapy of NIHL.
PMID: 32725028 [PubMed – as supplied by publisher]
Hough Ear Institute receives $300K grant to support research treatments for hearing loss
https://okcfox.com/news/local/hough-ear-institute-receives-300k-grant-to-support-research-treatments-for-hearing-loss
Hough Ear Institute receives $300K grant to support research treatments for hearing loss
Pathophysiological changes in inner hair cell ribbon synapses in the ageing mammalian cochlea
https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/JP280018
Pathophysiological changes in inner hair cell ribbon synapses in the ageing mammalian cochlea
Jing‐Yi Jeng Federico Ceriani Jennifer Olt Steve D. M. Brown Matthew C. Holley Michael R. Bowl Stuart L. Johnson Walter Marcotti
First published: 25 July 2020 https://doi.org/10.1113/JP280018
Intrinsic noise improves speech recognition in a computational model of the auditory pathway [Preprint]
https://www.biorxiv.org/content/10.1101/2020.03.16.993725v2
Intrinsic noise improves speech recognition in a computational model of the auditory pathway
Achim Schilling, Richard Gerum, Alexandra Zankl, Claus Metzner, Andreas Maier, Patrick Krauss
doi: https://doi.org/10.1101/2020.03.16.993725
How Artificial Intelligence Could Completely Restore Hearing: Lip-reading AI and Elon Musk’s “Neuralink” could deliver near-perfect audio and skip the ear entirely
https://www.hearingtracker.com/news/how-artificial-intelligence-could-completely-restore-hearing
How Artificial Intelligence Could Completely Restore Hearing
Lip-reading AI and Elon Musk’s “Neuralink” could deliver near-perfect audio and skip the ear entirely
Pipeline Therapeutics Initiates Phase 1/2a Clinical Trial of PIPE-505 in Sensorineural Hearing Loss – Topline results expected in early 2021…
https://www.pipelinetherapeutics.com/news/pr_07-23-2020.php
Pipeline Therapeutics Initiates Phase 1/2a Clinical Trial of PIPE-505 in Sensorineural Hearing Loss
PIPE-505 is the first small molecule developed specifically for the treatment of sensorineural hearing loss (SNHL) associated with speech-in-noise impairment
Topline results expected in early 2021
SAN DIEGO, July 23, 2020 – Pipeline Therapeutics, a biopharmaceutical company focused on the development and commercialization of first-in-class small molecules for neuroregeneration, today announced the initiation of a Phase 1/2a trial of the company’s lead product candidate, PIPE-505, a small molecule gamma secretase inhibitor (GSI), in sensorineural hearing loss (SNHL) associated with hearing speech in noisy environments.
Restoring hearing in mice
https://www.nature.com/articles/s41684-020-0605-2
In Brief
Published: 23 July 2020
GENE EDITING
Restoring hearing in mice
Alexandra Le Bras
Lab Animal volume 49, page220(2020)Cite this article
18 Accesses
Metricsdetails
Yeh, W-H. et al. Sci. Transl. Med. 12, eaay9101 (2020)
Genetic defects are a major cause of hearing loss (HL) in newborns. No curative treatments are available for genetic HL, but gene therapy-based strategies that replace an absent gene product or silence a pathological allele have shown promising results in mouse models.
A study describes a new base-editing approach aimed at correcting a point mutation in Tmc1 that causes deafness in Baringo mice. Adeno-associated virus (AAV) delivery of a cytosine base editor and guide RNA into the inner ears of Baringo mice at postnatal day 1 successfully corrected the Tmc1 mutation and partially rescued auditory function, thereby demonstrating the potential of base editing as a treatment for HL caused by recessive loss-of-function point mutations.
Antioxidants and Vasodilators for the Treatment of Noise-Induced Hearing Loss: Are They Really Effective?
https://www.frontiersin.org/articles/10.3389/fncel.2020.00226/full
https://www.ncbi.nlm.nih.gov/pubmed/32792910?dopt=Abstract
Related Articles
Antioxidants and Vasodilators for the Treatment of Noise-Induced Hearing Loss: Are They Really Effective?
Front Cell Neurosci. 2020;14:226
Authors: Alvarado JC, Fuentes-Santamaría V, Juiz JM
Abstract
We live in a world continuously immersed in noise, an environmental, recreational, and occupational factor present in almost every daily human activity. Exposure to high-level noise could affect the auditory function of individuals at any age, resulting in a condition called noise-induced hearing loss (NIHL). Given that by 2018, more than 400 million people worldwide were suffering from disabling hearing loss and that about one-third involved noise over-exposure, which represents more than 100 million people, this hearing impairment represents a serious health problem. As of today, there are no therapeutic measures available to treat NIHL. Conventional preventive measures, including public awareness and education and physical barriers to noise, do not seem to suffice, as the population is still being affected by damaging noise levels. Therefore, it is necessary to develop or test pharmacological agents that may prevent and/or diminish the impact of noise on hearing. Data availability about the pathophysiological processes involved in triggering NIHL has allowed researchers to use compounds, that could act as effective therapies, by targeting specific mechanisms such as the excess generation of free radicals and blood flow restriction to the cochlea. In this review, we summarize the advantages/disadvantages of these therapeutic agents, providing a critical view of whether they could be effective in the human clinic.
PMID: 32792910 [PubMed]
Inner Ear Gene Therapies Take Off: Current Promises and Future Challenges
https://www.mdpi.com/2077-0383/9/7/2309/htm
https://pubmed.ncbi.nlm.nih.gov/32708116/
Inner Ear Gene Therapies Take Off: Current Promises and Future Challenges
by Sedigheh Delmaghani *OrcID andAziz El-Amraoui *OrcID
Progressive Sensory Disorders, Pathophysiology and Therapy Unit, Institut Pasteur, Institut de l’Audition, INSERM-UMRS1120, Sorbonne Université, 63 rue de Charenton, 75012 Paris, France
Authors to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(7), 2309; https://doi.org/10.3390/jcm9072309
Received: 27 June 2020 / Revised: 13 July 2020 / Accepted: 15 July 2020 / Published: 21 July 2020
