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Neuracle Science Initiates Phase 1/2 Clinical Trial of NS101 for the Treatment of Hearing Loss

First details on NS101, a new pipeline candidate for sensorineural hearing loss (previously “undisclosed indication”), from Neuracle Science.

A new phase 1/2 clinical trial of NS101 for the treatment of hearing loss was added to clinicaltrials.gov on February 8, 2024. The trial, titled A Phase 1b/​2a, Study Evaluating the Safety, PK/​PD and Efficacy of NS101 in Healthy Volunteers and SSNHL Patients, lists a start date of January 19, 2024. The study record and public details only emerged more than a month later, however.

Here is what we know so far:

This new trial is currently recruiting participants and the sponsor, Neuracle Science, plans to enroll a total of 118 participants across 16 locations.

Important point: although the study is evaluating NS101 for SSNHL (sudden sensorineural hearing loss), the testing on healthy volunteers is not without significance. The drug’s potential applications extend beyond sudden/acute situation, and it is not limited to the “rescue therapy” category of treatment.

From the official clinical trial record (NCT06249919):

“NS101 is an anti FAM19A5 antibody expected to play as a synapse organizer and reversing synapse dysfunction in various neurological diseases.”

What else do we know about NS101—and its “regenerative” potential?

NS101 is an investigational new treatment that promotes nerve synapses and nerve regeneration. It’s being developed by Neuracle Science Co., Ltd., in collaboration with Samsung and Korean University. This broad applicability to nerve synapses and regeneration means that NS101 is also being researched to help with degenerative neurological diseases such as Alzheimer’s disease, ALS, and acute spinal cord injury. This means that NS101 may also help with other synaptopathies as well as different kinds of sensorineural hearing loss (not just the sudden sensorineural hearing loss being studied in this particular trial).

This is also supported by clues from the official trial record—note the provided keywords:

NS101 hearing loss indications trial record list
Specific keywords provided by Neuracle Science, relating to study and beyond “sudden” hearing loss.

Last year, on January 26, 2023, the company shared a press release outlining positive results of its first-in-human phase 1 clinical trial of NS101. That trial showed that the treatment had a good safety profile and “robust FAM19A5 target engagement.”

“Neuracle Science (CEO: Dr. Jae Young Seong) announced top-line results from the Phase 1 study of NS101, an investigational monoclonal antibody for the treatment of neurological diseases. NS101 binds to and neutralizes FAM19A5/TAFA5, a potential target for synaptopathy.”

At that time, Neuracle Science also shared that they planned “to initiate further clinical trials with an undisclosed indication…” Based on this phase 1/2 trial development, that undisclosed indication mentioned last year appears to have been hearing loss (plus tinnitus—but more about that later).

The Neuracle Science company website also has some more information, though its website has not yet been updated to cover the hearing loss indication(s). Note: This is not uncommon for small/private biotech companies, as they are usually too busy focusing on the research to update their pipeline snapshot. The company might post an update soon — hopefully one with a deeper dive into the mechanism of NS101 for various forms of sensorineural hearing loss.

The website has not yet been update to include the sensorineural hearing loss research angle.

http://www.neuracles.com/?version=135&spkey=5b3a3e4874f80210e3b655253439c7e702c29894&module=true&PageAccess=main/pipeline#sec01

Quick background on Neuracle Science, the company behind NS101:

According to last year’s press release, “Neuracle Science is a clinical-stage biotech company specializing in the development of new drugs for the treatment of neurological diseases.”

Here is some additional information about Neuracle Science:

Neuracle Science logo
Logo as it appears on the company website, neuracles.com.

http://www.neuracles.com/?version=135&spkey=5b3a3e4874f80210e3b655253439c7e702c29894&module=true&PageAccess=main/neuracle

What type of drug is NS101?

  • IV infusion
  • Doses = 15 mg/kg or 30 mg/kg
  • Frequency = Every second week over the course of 12 weeks
  • Participants will be followed for up to 20 weeks

In addition to testing for safety and tolerability, this study will look at whether NS101 is effective in improving hearing in people with sudden sensorineural hearing loss who have not benefited from treatment with oral steroids. This clinical trial is set up to be placebo-controlled and double-blinded.

Researchers will be looking for improvements in these outcomes:

  • Hearing capacity (via Pure Tone Audiometry, ABR, DPOAE, ECochG)
  • Speech discrimination (via SRT, SDS)
  • Tinnitus (via THI, VAS)

Looking further ahead, the anticipated completion date for the study is June 19, 2025.

Here is the link to the official study record for A Phase 1b/2a, Double-blinded, Placebo-controlled, Multiple Doses, 2 Step-up Study Evaluating the Safety, Tolerability, PK/PD and Efficacy of Systemic NS101 in Healthy Volunteers and SSNHL Patients—last updated on February 8, 2024:

https://clinicaltrials.gov/study/NCT06249919

How to get email updates on the development of NS101

If you want updates on NS101 from Neuracle Science — including the progress of this new clinical trial — sign up for the Hearing Loss Treatment Report email newsletter.

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It’s free, your information is kept private, and you can unsubscribe at any time with a single click. As a subscriber, you get early access to “first look” updates like this one — before they are added to the front page of this website (or anywhere else).

Expect between 1-2 emails per week… but only if something interesting and treatment-related is happening.

References

https://classic.clinicaltrials.gov/ct2/show/NCT06249919

https://www.linkedin.com/feed/update/urn:li:activity:7024192632750829569/?updateEntityUrn=urn%3Ali%3Afs_feedUpdate%3A%28V2%2Curn%3Ali%3Aactivity%3A7024192632750829569%29

http://www.neuracles.com/?version=135&spkey=5b3a3e4874f80210e3b655253439c7e702c29894&module=true&PageAccess=main/neuracle

http://www.neuracles.com/?version=135&spkey=5b3a3e4874f80210e3b655253439c7e702c29894&module=true&PageAccess=main/pipeline#sec01

Eli Lilly-Backed Audion Therapeutics Initiates Phase 2 Clinical Trial of AUD1001 (LY3056480) in Patients with Sensorineural Hearing Loss

The official record for the study, “A Phase 2 Double Blind, Randomized, Placebo Controlled Trial inVEstigating the Effect and Safety of Several Dosing Regimens of LY3056480 in Patients With STAble Sensorineural Hearing Loss”, was added to ClinicalTrials.gov on September 30, 2021.

The name of this new study is “VESTA”, the name of the drug is “AUD1001” (also known as “LY3056480”), and it is sometimes referred to as the “REGAIN treatment” for hearing loss.

aud1001 study record phase 2 teaser

Official description from the new study record (9/30/2021):

VESTA is a double blinded, randomized, placebo controlled, multi center efficacy phase 2 study comparing three dosing regimens of 250 µg LY3056480. Adult volunteers with stable mild to moderately-severe SNHL will be recruited through Adult Otolaryngology – Head & Neck Surgery Services in the US. Four injections of 250µg LY3056480 or placebo administered trans-tympanically into one ear (worse hearing ear).

Source —link to the study record:

LY3056480 in Patients with Sensorineural Hearing Loss (NCT05061758)
https://clinicaltrials.gov/ct2/show/NCT05061758

More background and context — from Audion’s website:

AUD1001 was shown to be safe and well tolerated, and provided early indications of efficacy in speech in noise, a key clinical outcome parameter. Importantly, the efficacy signals persisted a year after the treatment.

[…]

Audion is preparing for initiation of new clinical trials of AUD1001 for sensorineural hearing loss at multiple sites in Europe and in the US in H2 2021. The planned Phase 2b double blind, placebo controlled trials will be conducted in adults with demonstrated loss of clarity, using a standardized local drug delivery.

Source: https://audiontherapeutics.com/development/

More details about the AUD1001 study:

  • phase 2 study will enroll 135 participants
  • recruitment has NOT started yet
  • three recruitment locations listed so far: Illinois, New York, Virginia
  • company website mentions sites in Europe but the study record says participants will be recruited through sites in the US
  • that does not rule out Europe sites (since the study record could be updated when new sites are added in the future)
  • so, right now there is a slightly confusing inconsistency — but nothing is contradictory or set in stone

As for timeline…

  • Start Date: September 2022
  • Primary Completion Date : September 2024
  • Study Completion Date : March 2025

Keep in mind, these are Estimated dates, and subject to change.

The key date here, for most people, is the September 2022 start date.

As for when RECRUITING will begin…

Not sure yet.

But I will send out an email when the status changes from “Not yet recruiting” to “Recruiting” — as soon as I find out. Nothing to report just yet and no estimates or opinions to share.

If you are not subscribed and want AUD1001 updates, I have a strongly-biased (and very good) recommendation: subscribe to the Hearing Loss Treatment Report email newsletter. Email updates for people who want “early access” to hearing loss treatment updates — like this one about AUD1001… in many cases, before the company has had time to issue a press release! (That is what happened here.) Expect between 1-3 emails per week, on average. Sometimes none. Sometimes four. It depends. But the important thing is, issues are only sent when something exciting and new is happening. No recycled stories or press releases. No blogspam. No advertorials or sneakiness. No spam, no nonsense. Unsubscribe instantly with one click.

More AUD1001 updates to follow… including an update whenever the trial opens its doors and begins recruiting. Which, hypothetically, could be any day now.

Sneak preview of AP-001, a novel therapeutic for hearing loss from Anida Pharma

Some early details on AP-001 (also known as neuroprotectin D1 or NPD1), a novel therapeutic currently being studied by Anida Pharma to treat noise-related and age-related hearing loss.

AP-001 anida pharma pipeline hearing loss july 2021 annotated

Background:

Anida Pharma is a private biotech company based in Cambridge, Massachusetts, focused on developing new drugs “to prevent and restore sensory organ dysfunction.”

The company’s lead drug candidate is a compound called “AP-001” and… what makes AP-001 special is that it works on multiple pathways all at once: e.g., “inflammation, cell death and tissue repair, both epithelial and nerve regrowth” — all of which are known to be associated with hearing impairment, to different degrees, in varying contexts.

AP-001 (also known as neuroprotectin D1 or NPD1), it seems, has the potential to treat hearing loss — including noise-related, drug-related, and/or age-related causes.

Rough draft copy of explanation [work-in-progress]:

Worth mentioning: AP-001 is endogenous. In other words, the body makes it naturally. And, even more interesting, is the role it plays…

Basically, AP-001’s normal job is to clean up any messes caused by the body’s immune system. So the body’s immune system recognizes a threat. Attacks said threat. And sometimes there is a mess. Collateral damage. Well, when that happens, the body releases AP-001… which is deployed to fix, repair, restore any destruction caused during the immune response and battle.

You can think of AP-001 as the body’s own cleanup crew… and a function within the body that has evolved as a tool to repair the chaos and damage following a immune attack damage. It is referred to as a “counter-mechanism” in the science section of the Anida Pharma website. I like that.

Anyway, the main reason this counter-mechanism exists is… because the body wants to make sure important functions (such as sight or hearing) are not permanently lost after getting caught up in the crossfire of an immune system battle.

And so, a special mechanism evolved to handle that “messy” repair and cleanup job. Before the damaged system collapsed to a point of no return.

Now, here is how this relates to hearing restoration…

Scientists believe they have discovered a way to harness that “counter-mechanism” and its special “rebuilding” toolset… and extend its purpose beyond that of “clean up crew” in wake of a big immune system battle… and instead deploy it in response to any sort of damage, for various purposes.

So, with respect to hearing loss… the “repair job” could be using AP-001 to fix any sort of trauma or loss… not just an immune warzone… e.g. it could be noise trauma, ototoxicity/drug-induced, or even be used to reverse age-related damage and progression.

The idea here is, this natural “counter-mechanism” (a.k.a. AP-001) might still be effective beyond its original duty (which was limited to immune attack rebuilding)… and applicable to situations where it might not have been released naturally, in great enough volume.

[DRAFT]

Some hearing loss-related tidbits from the official Anida Pharma company website:

“Anida is also working at identifying treatments to restore the hearing in individuals suffering age- and noise-related hearing loss.”

“Anida is a preclinical-stage biopharmaceutical company leveraging the knowledge around the body’s own homeostatic and protective mechanisms to develop targeted therapeutics in the fields of vision and hearing.”

“AP-001, is an endogenous lipid-derived agonistic small molecule from the DHA metabolome.”

Le “annotated Anida Pharma pipeline” snapshot:

AP-001 anida pharma pipeline hearing loss july 2021 annotated
Much wow. Such pipeline.

(Image credit and source of original image: https://www.anidapharma.com/)

This article is a work in progress. [Last updated on 7/25/2021 at 5:09pm EST.] For now, I just wanted to share news of “AP-001” ASAP and add it to the hearing loss treatment radar. (So more people know that it exists.) Also…

Remember to subscribe if you want early access to updates on stuff like this. See link below. (Email subscribers receive links to articles like this one several days before the article is added to the front page of this website.)

AP-001 updates

Sign up for the Hearing Loss Treatment Report email newsletter to get updates on promising new hearing loss drugs on the horizon. It’s free, your information is kept private, you will not receive promotional emails, and you can easily unsubscribe at any time with one click. Expect between 1-2 emails per week, but only if something interesting is happening.

References

KCNQ4 Activators as a Potential Treatment for Hearing Loss

A recently published special issue of International Journal of Molecular Science reviewed a variety of therapeutic interventions currently being studied as novel strategies to restore hearing.

One of these strategies involves the use of “KCNQ4 activators” as a way to keep the inner ear functioning properly. And according to the paper, existing drugs (or combinations thereof) that are already approved could potentially be repurposed as therapies for sensorineural hearing loss.

From the May 26, 2021 paper titled, “Molecular Mechanisms of Sensorineural Hearing Loss and Development of Inner Ear Therapeutics”:

The voltage-gated potassium channel KCNQ4 has an essential role in regulating auditory function in the inner ear, by contributing to potassium recycling and maintenance of cochlear homeostasis. Reduced activity of the KCNQ4 channel has been associated with a genetic form of hearing loss, noise-induced hearing loss, and age-related hearing loss. Rim and colleagues presented a comprehensive review of 90 publications looking at the KCNQ4 as a potential therapeutic target for the treatment of hearing loss. In this review, the authors updated the current concepts of the physiological and pathophysiological roles of KCNQ4 in the inner ear and focused on the role of KCNQ4 activators in therapeutic management of different forms of hearing loss. They propose that the simultaneous application of two activators with distinct modes of action may result in synergistic effects and reduced off-target effects. It was also suggested that drug repurposing may be an attractive option for clinical development of KCNQ4 activators as therapies for hearing loss.

Another recent paper, from three months ago (published March 2, 2021) titled, “Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss”, stated:

Therefore, the discovery of small compounds activating or potentiating KCNQ4 is an important strategy for the curative treatment of hearing loss.

The authors concluded by recommending that “KCNQ4 activators should be validated in clinical trials, as there is no ongoing clinical trial targeting hearing loss by KCNQ4 activators currently.”

But do not let the fact that KCNQ4 activators have not yet entered human clinical trials mislead you. Despite the current lack of trials, that does not automatically mean these drugs are far, far away.

Because, as the authors also pointed out earlier in the same paper: “Drug repurposing and optimization for applicable specific KCNQ4 mutation might also be an option for clinical application of KCNQ4 activators […] with advantages of reducing the cost and shortening the time when compared to de novo drug discovery.”

As far as what to keep an eye out for next, on the topic of KCNQ4, the researchers also tip us off as to which company is working on this mechanism most closely:

Acousia Therapeutics, which is a biotech company aiming for the development of small-molecule drugs for sensory neuronal hearing loss, has eight compounds targeting KCNQ4 in its pipeline.

Company website here (comment: Acousia seems to keep a low profile, so for now don’t expect to find any additional details about these eight compounds): http://www.acousia.com/

Last but not least, a fun fact.

Aside from the repurposed drugs that might hold hearing restoration potential, there is another compound related to KCNQ4 mentioned in the paper. An exotic one, as described in one of the cited papers: Subtype-Selective Activation of Kv7 Channels by AaTXKβ(2–64), a Novel Toxin Variant from the Androctonus australis Scorpion Venom.

Scorpion venom. Hmmm…

AUTHOR’S NOTE: There is something oddly reassuring about the thought of researchers from around the world leaving no stone unturned (and no tiny venomous creature unexamined) in search of a potential hearing loss cure.

A good reminder that we never know where (or from what) the next big discovery will arise. Nature is full of secrets and science is constantly uncovering these surprises…

KCNQ4 activators meme hearing loss scorpion

More updates to follow…

How to get KCNQ4 activator updates

  • Join the free email newsletter to get updates related to repurposed drugs targeting KCNQ4 (plus, news about other promising treatments in development for hearing restoration). Expect between 1 and 3 emails per week. But only when something interesting appears on the radar. No spam, no promotional emails, no third parties, and one-click unsubscribe. Privacy respected.

References

Inhalation of Molecular Hydrogen, a Rescue Treatment for Noise-Induced Hearing Loss

CATEGORY:
Research

SCREENSHOT:
Inhalation of Molecular Hydrogen, a Rescue Treatment for Noise-Induced Hearing Loss

TITLE:
Inhalation of Molecular Hydrogen, a Rescue Treatment for Noise-Induced Hearing Loss

CONTENT:
Front Cell Neurosci. 2021 Jun 1;15:658662. doi: 10.3389/fncel.2021.658662. eCollection 2021.

ABSTRACT

Noise exposure is the most important external factor causing acquired hearing loss in humans, and it is strongly associated with the production of reactive oxygen species (ROS) in the cochlea. Several studies reported that the administration of various compounds with antioxidant effects can treat oxidative stress-induced hearing loss. However, traditional systemic drug administration to the human inner ear is problematic and has not been successful in a clinical setting. Thus, there is an urgent need to develop rescue treatment for patients with acute acoustic injuries. Hydrogen gas has antioxidant effects, rapid distribution, and distributes systemically after inhalation.The purpose of this study was to determine the protective efficacy of a single dose of molecular hydrogen (H2 ) on cochlear structures. Guinea pigs were divided into six groups and sacrificed immediately after or at 1 or 2 weeks. The animals were exposed to broadband noise for 2 h directly followed by 1-h inhalation of 2% H2 or room air. Electrophysiological hearing thresholds using frequency-specific auditory brainstem response (ABR) were measured prior to noise exposure and before sacrifice. ABR thresholds were significantly lower in H2 -treated animals at 2 weeks after exposure, with significant preservation of outer hair cells in the entire cochlea. Quantification of synaptophysin immunoreactivity revealed that H2 inhalation protected the cochlear inner hair cell synaptic structures containing synaptophysin. The inflammatory response was greater in the stria vascularis, showing increased Iba1 due to H2 inhalation.Repeated administration of H2 inhalation may further improve the therapeutic effect. This animal model does not reproduce conditions in humans, highlighting the need for additional real-life studies in humans.

PMID:34140880 | PMC:PMC8205059 | DOI:10.3389/fncel.2021.658662

SOURCE:
Frontiers in cellular neuroscience

PUBLISHER:

PMID:
pubmed:34140880

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:34140880

DOI:
10.3389/fncel.2021.658662

DATE – PUBLISHED:
Fri, 18 Jun 2021 06:00:00 -0400

DATE – DOI:
2021-06-01T05:34:01Z

DATE – ADDED:
06/18/21 01:25PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34140880/

LINK – DOI:
https://doi.org/10.3389/fncel.2021.658662

LINK – PUBLISHER:
https://www.frontiersin.org/articles/10.3389/fncel.2021.658662/full?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-06-18T17:25:36+00:00, https://www.hearinglosstreatmentreport.com.

Effects of Insulin-Like Growth Factor (IGF-1) in Patients with Sensorineural Hearing Loss

CATEGORY:
Research

SCREENSHOT:
Effects of Insulin-Like Growth Factor (IGF-1) in Patients with Sensorineural Hearing Loss

TITLE:
Effects of Insulin-Like Growth Factor (IGF-1) in Patients with Sensorineural Hearing Loss

CONTENT:
J Int Adv Otol. 2021 May;17(3):207-214. doi: 10.5152/iao.2021.8549.

ABSTRACT

OBJECTIVES: (1) To test the effect of local administration of insulin-like growth factor-1 (IGF-1) in patients with sensorineural hearing loss (SNHL). (2) To test the effect of local administration of IGF-1 in patients with ototoxicity.

METHODS: Forty patients with SNHL were included in the study. Their hearing thresholds at different frequencies (0.5, 1, 2, and 4 kHz) along with the average hearing threshold were noted. The patients were then randomly allocated to 2 groups and were treated with IGF-1 via one of the following routes: (1) intratympanic injection and (2) Gelfoam. Patients were followed-up at weekly intervals for 6 weeks but follow-up PTA was done at 3 weeks, 6 weeks, and 6 months only.

RESULTS: Forty patients (25 male, 15 female) participated in the study. Their age ranged from 13 to 63 years, with a mean of 31.3 years. Nineteen (47.5%) patients exhibited some degree of recovery after 6 months of follow-up, while 21 (52.5%) did not exhibit any recovery. Fourteen (35%) patients showed slight recovery (SR), 1 (4%) patient showed marked recovery, and complete recovery was observed in 4 (10%) patients. Twelve of the 20 patients who underwent treatment using Gelfoam showed improvement in hearing (measured as a reduction in hearing threshold), while only 7 of the 20 patients who underwent intratympanic injection showed such improvement. Among adverse reactions, the most common was pain (88%) which typically did not last beyond 3 days. Other adverse reactions observed were dizziness (24%) and headache (20%). One patient suffered from acute suppurative otitis media (ASOM) and had a perforation in the tympanic membrane. However, this was treated successfully with medications.

CONCLUSION: Intratympanic IGF-1 is a novel drug that has shown early promise in controlling and reversing SNHL.

PMID:34100744 | DOI:10.5152/iao.2021.8549

SOURCE:
The journal of international advanced otology

PUBLISHER:

PMID:
pubmed:34100744

ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:34100744

DOI:
10.5152/iao.2021.8549

DATE – PUBLISHED:
Tue, 08 Jun 2021 06:00:00 -0400

DATE – DOI:
2021-06-04T13:09:30Z

DATE – ADDED:
06/08/21 02:54PM

LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/34100744/

LINK – DOI:
https://doi.org/10.5152/iao.2021.8549

LINK – PUBLISHER:
https://www.advancedotology.org/en/effects-of-insulin-like-growth-factor-igf-1-in-patients-with-sensorineural-hearing-loss-131632?utm_source=hearinglosstreatmentreport.com

IMAGE:

REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2021-06-08T18:54:02+00:00, https://www.hearinglosstreatmentreport.com.

CMS121, a fatty acid synthase inhibitor, reduced hearing loss and increased preservation of ribbon synapses in the mid-range frequencies

A noteworthy abstract from The Association for Research in Otolaryngology (ARO) 44th Annual MWM held a few months ago:

Attenuation of Age-Related Hearing Loss in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice Treated With Fatty Acid Synthase Inhibitor CMS121

Background

The senescence-accelerated prone strain 8 (SAMP8) mouse model provides opportunities to investigate potential therapies for age-related hearing loss (ARHL), the most common sensory disorder in older humans. In SAMP8 mice, oxidative stress leads to chronic inflammation, apoptosis, and premature senescence. CMS121 is a fatty acid synthase inhibitor previously shown to improve cognitive function in SAMP8 mice through anti-inflammatory and antioxidative effects in the hippocampus. Given the common cellular pathways leading to age-related dysfunction inthe hippocampus and cochlea, the aim of our study is to determine whether CMS121 is protective against ARHL in SAMP8 mice.

Methods

Auditory brainstem responses (ABRs) across six frequencies (4, 8, 12, 16, 24, and 32 kHz) were used to assess baseline hearing in sixteen 4-week-old SAMP8 mice, which were then split into age-matched groups with similar average hearing thresholds. The control group was then fed a vehicle diet, while the experimental group was fed a diet with CMS121. ABR measurements were repeated at seven, ten, and thirteen weeks of age. Cochlear immunohistochemistry was then performed using Ctbp2, GluR2, and Myo7a to analyze the number of paired ribbon-receptor synapses per inner hair cell (IHC). Descriptive statistics are provided with mean ±SEM (Standard Error of the Mean). Two-sample t-tests were performed to compare hearing thresholds and paired synapse count across the two groups, with alpha = 0.05.

Results

Baseline hearing thresholds across the six frequencies in the control group (77.5± 5.9, 59.0 ± 9.5, 44.2 ± 6.1, 47.5 ± 7.8, 36.8 ± 6.0, and 35.0 ± 7.2) were statistically similar to those of the CMS121 group (74.9 ± 2.3, 51.4 ± 3.7, 42.3 ± 3.3, 45.8 ± 5.0, 37.8 ± 4.6, and 33.3 ± 4.7.) While the control group showed progressive ARHL (hearing thresholds at 13 weeks were 84.0 ± 6.4, 63.8 ± 10.0, 56.5 ± 6.1, 64.8 ± 7.4, 37.0 ± 6.4, and 38.3 ± 6.1), the CMS121 group maintained stable hearing thresholds at 13 weeks (73.1 ± 4.0, 50.0 ± 4.5, 39.8 ± 3.8, 43.8 ± 4.4, 31.6 ± 4.3, and 35.8 ± 7.1). At that time, the control group had significantly worse hearing thresholds at 12 kHz (56.5 vs. 39.8, p = 0.044) and 16 kHz (64.8 vs. 43.8, p = 0.040) compared to the CMS121 group. Immunohistochemistry showed a significantly lower synapse count per IHC in the control group (15.7) compared to the CMS121 group (18.4), p = 0.014.

Conclusions

Our study shows a significant reduction in hearing loss and increased preservation of ribbon synapses in the mid-range frequencies among mice treated with CMS121 compared to untreated mice. These findings support expanding the scope of current research on CMS121 to further investigate the promising role of this compound as a protective agent against ARHL.

Further study will be needed to explore whether CMS121 can reverse any pre-existing hearing loss. But considering how nearly all forms of hearing loss are progressive (albeit some are slower than others), a decibel saved is a decibel earned gained.

As far as mechanism is concerned, it seems to show potential in combating the damaging effects of noise-induced lipid peroxidation. But there’s likely a few things going on.

“But human trials must be years away.”

Fortunately this drug candidate has a bit of a head start, as it is being studied in Alzheimer’s disease:

https://www.sciencedirect.com/science/article/pii/S2213231720308533

That’s all for now. More information to follow.

These unfinished notes on CMS121 are for email subscribers. Sign up here.

Vinpocetine Improves Hearing in Patients with Sensorineural Hearing Loss: Results from a Phase 2 Study

New findings published in the Journal of Pharmacological Sciences outline the effectiveness of vinpocetine, a sodium channel blocker, as a treatment for sensorineural hearing loss.

“…with the use of vinpocetine, the hearing capacity improved. It is concluded that vinpocetine helps to stop hearing impairment and even improve hearing.”

Source: J Pharmacol Sci. 2021 Apr;145(4):313-318. doi: 10.1016/j.jphs.2021.01.010. PMID: 33712282.

Researchers conducted a phase 2 trial to determine if treatment with 30mg/day of vinpocetine could stop or reverse hearing deterioration in patients with sensorineural hearing loss.

Quick background from Wikipedia:

“Vinpocetine (ethyl apovincaminate) is a synthetic derivative of the vinca alkaloid vincamine. Vincamine is extracted from either the seeds of Voacanga africana or the leaves of Vinca minor (lesser periwinkle).”

Obligatory photo of the flowering plant:

periwinkle photo
“Lesser Periwinkle (Vinca minor)” (Photo credit: Ryan Kaldari)

More information:

The results, which were recently printed in the April issue of JPS, in a paper titled, “Evaluation of vinpocetine as a therapy in patients with sensorineural hearing loss: A phase II, open-label, single-center study”, appear promising.

Here is the abstract (emphasis ours):

Abstract
The progressive degeneration of the excitable cells of the ear depends on the sustained excitation of the voltage-sensitive sodium channels, so the negative pharmacological modulation could be a rational therapeutic strategy against the damage of these cells. The objective was to demonstrate the effectiveness of Vinpocetine (VPC), a potent sodium channel blocker, as a treatment for acquired sensorineural hearing loss. A phase II, longitudinal and prospective open clinical study, was conducted over a period of 12 months with patients older than 18 years, to demonstrate the effectiveness of Vinpocetine (VPC) as a treatment for acquired sensorineural hearing loss, using evoked potentials, otoacoustic emissions, audiometry and logoaudiometry, analyzing the results at 6 and 12 months of treatment with Vinpocetine (30 mg/day in 3 doses). It was observed that from 0 to 6 months there was hearing impairment (which was already expected due to the age of the patients). From 6 to 12 months and from 0 to 12 months there were significant differences with a tendency towards improvement, indicating that the aforementioned deterioration not only stopped, but that with the use of vinpocetine, the hearing capacity improved. It is concluded that Vinpocetine helps to stop hearing impairment and even improve hearing.

Link to the full-text version of the paper plus a backup link to the entry on PubMed:

Journal of Pharmacological Sciences front cover
Journal of Pharmacological Sciences (JPS) is an international open access journal that publishes research on “novel and exciting pharmacological findings.” (Source: ScienceDirect)

More information on vinpocetine will follow.

For now, here are some quick notes followed by links to further reading:

  • semisynthetic natural product
  • derived from the periwinkle plant
  • has anti-inflammatory properties
  • has the ability to modulate sodium and channel channels
  • is used as a vasodilator for cerebrovascular and age-related memory disorders
  • regulates levels of toll-like receptors
  • subject of debate, controversy, and FDA activity/memos [comment: to anyone reading this, be very careful of vinpocetine for sale on the internet. This article is not meant to suggest any treatment and especially not a do-it-yourself vinpocetine regimen. Furthermore, one of the studies I read tested supplement products that listed  vinpocetine as an ingredient… and found that many of these products actually contained no vinpocetine (and/or worse, “replacement” ingredients that were not listed on the bottle).]
  • a search for vinpocetine on PubMed shows a lot of results, quite recent too… hmmm…

Some interesting articles on vinpocetine [author’s note: this “drug” keeps getting more interesting the more I read about it…]:

Two more scientific papers, related to vinpocetine and the auditory system:

That’s all for now.

Michael Sutton

P.S. This article is a DRAFT COPY (work in progress). An early access link is provided to HearingLossTreatmentReport.com email subscribers. Not signed up? It’s free. Subscribe to the newsletter here »

P.P.S. You can email me at michael@urgentresearch.com if you have feedback/comments or just want to say hello.

FGF signaling system for hearing restoration

Researchers at the University of Utah’s Mansour Lab are studying the Fibroblast Growth Factor signaling pathway with the long-term goal of harnessing developmental signals to drive hearing restoration.

“Our results will contribute new knowledge to the long-term goal of harnessing developmental signals to drive hearing restoration.”

The project has received funding from the National Institute on Deafness and Other Communication Disorders (NIDCD) and will continue through January 2022.

According to investigators, the results “will facilitate future efforts to manipulate the FGF signaling system for hearing restoration.”

First, they will use mouse models to investigate the role of the Fibroblast Growth Factor signaling pathway and its critical role in the inner ear.

But the findings could uncover key development signals that could potentially be commandeered to restore hearing function.

Dr. Mansour photo
TEAM LEADER a.k.a. Professor Mansour (Photo credit: University of Utah website)

The team is being led by Dr. Suzanne L. Mansour (Molecular Biology Program – FGFs and Inner Ear Development, Mouse models of hearing loss and restoration), who has been studying these FGF signals since the early 2000s.

Here is the full abstract and public health relevance statement:

Regulation of inner ear development by FGF signals and effectors

Mansour, Suzanne L.
University of Utah, Salt Lake City, UT, United States

Abstract

Morphogenesis of the inner ear epithelium requires coordinated deployment of several signaling pathways and disruptions cause abnormalities of hearing and/or balance. With the advent of cochlear implantation to treat hearing loss even in cases of inner ear malformation, it is critical to understand exactly how such malformations affect the auditory ganglia and innervation. Also, in light of the intense focus on in vitro generation of inner ear cell types for transplantation and in vivo manipulation of developmental signaling molecules to promote differentiation of various inner ear cells for hearing restoration, elucidating the roles and regulation of such signals and their effectors governing otic differentiation and morphogenesis are necessary to advance treatment. The genes encoding FGF3 and FGF10, ligands that signal through FGFR2b and FGFR1b, are expressed dynamically throughout otic development in both epithelial and ganglion domains. Studies conducted by the Mansour Lab of both conventional Fgf3 and Fgf10 conditional knockout mice and those expressing a doxycycline-inducible ligand trap (dnFGFR2b) that rapidly inhibits signaling through both FGFR1b and FGFR2b, showed that Fgf3 and Fgf10 are not required in the placode lineage for otocyst formation, but are required subsequently for otocyst patterning, neuroblast maintenance, epithelial proliferation and both vestibular and cochlear morphogenesis. Furthermore, the first genome wide analyses of otocyst mRNA revealed FGFR2b/1b signaling targets that define novel candidates for genes involved in otic morphogenesis and function. This proposal has two Aims addressing the hypotheses that 1) FGFR2b/1b signaling is required continuously for both otic neuroblast specification and maintenance, and that at later stages, mesenchymal signaling, as well as that in the epithelial and ganglion domains, is required for cochlear epithelial differentiation and ganglion maintenance and 2) FGFR2b/1b downstream target genes mediate some or all of the effects of FGFR2b/1b signaling on otic morphogenesis and gangliogenesis. To determine the early role of FGFR2b/1b signaling in otic ganglion formation and its later role in epithelial differentiation and ganglion maintenance, DOX-induced ubiquitous and CRE-limited expression of dnFGFR2b will be employed and morphology and molecular markers of otic patterning, proliferation and survival in both tissues will be assessed. To determine the roles of downstream targets of FGFR2b/1b signaling, two genes encoding transcription factors that are activated by FGFR2b/1b signaling and one gene encoding a BMP signaling regulator that is repressed by FGFR2b/1b signaling will be studied. Otic conditional mutants will be generated for each gene, and their morphologic and functional development will be assessed. In addition, the extent to which the BMP regulator contributes to the dnFGFR2b phenotypes and the effects of overexpressing the BMP regulator will be assessed. The results will contribute new knowledge that will facilitate future efforts to manipulate the FGF signaling system for hearing restoration.

Public Health Relevance

Permanent hearing loss caused by malformation of the inner ear or congenital or progressive loss of its sensory or neural cells affects up to one third of individuals by the age of 80 and generates significant social and healthcare costs. In this proposal, we use mouse models to investigate the role of the Fibroblast Growth Factor signaling pathway in forming the inner ear epithelium and neurons. Our results will contribute new knowledge to the long-term goal of harnessing developmental signals to drive hearing restoration.

For updates on Mansour’s FGF signaling system (and other hearing restoration research/treatments) sign up for free email updates (our newsletter) here.

References

Project #: 1R01DC019127-01

UC-Irvine researchers studying nicotine-like drugs to improve hearing and restore auditory function

Researchers at University of California-Irvine are testing the effects of nicotine to see if it will reduce or reverse auditory decline.

The research is part of a new project funded by the NIA division of the U.S. National Institutes of Health.

The project was recently awarded $640,473 in grant money for 2021 to determine, in humans and mice, whether nicotine’s effects can restore auditory function.

It began a few months ago and will continue until at least the end of 2021. (If successful, it could continue to receive more funding every year, until the end of 2025.)

Worth pointing out: nicotine, in this context, is NOT related to tobacco, smoking, or vaping. This is some sort of pharmaceutical nicotine, apparently:

“Because nicotine enhances cortical and cognitive function, pharmaceutical companies are developing nicotine-like drugs … These drugs are non-addictive (unlike nicotine in tobacco), yet nicotine also is non-addictive when given topically or orally.”

And, according to the project description, a positive outcome “will facilitate the translation of nicotine-based therapeutic treatments for hearing loss to clinical populations.”

Here is a shortened version of the project Abstract and Public Health Relevance Statement (formatting and emphasis ours):

Ideally, a combination of drug treatment with hearing aids and behavioral training could restore auditory function, but the development of pharmacological treatments requires a better understanding of the mechanisms by which candidate drugs improve hearing.

The goals of this proposal are to develop biomarkers of altered auditory processing in aging mice and humans, and using these biomarkers, to test the hypothesis that nicotine can normalize these age-related central auditory deficits.

Because nicotine enhances cortical and cognitive function, pharmaceutical companies are developing nicotine-like drugs to target cognitive deficits in aging. These drugs are non-addictive (unlike nicotine in tobacco), yet nicotine also is non-addictive when given topically or orally. However, its clinical benefits have not been exploited except as an aid to stop smoking.

We hypothesize that: 1) acute nicotine compensates for the age-related decline in inhibition by exciting the remaining inhibitory neurons; 2) chronic nicotine exposure (CNE) upregulates nicotinic acetylcholine receptors (nAChRs); and, as a result, 3) acute nicotine and/or CNE will reduce or reverse the age-related auditory decline.

We will test these hypotheses in both mouse and human at the level of cells (mouse in vitro brain slice), neural systems (mouse in vivo physiology; human brain imaging and EEG) and behavior (human psychoacoustics).

  • Aim 1 will determine in mouse whether age-related decline in auditory spectrotemporal processing is reversed by acute nicotine or CNE, and characterize the associated cellular mechanisms.
  • Aim 2 will identify, in humans, age-related changes in receptive field properties in auditory cortex using novel fMRI techniques and determine if nicotine reverses these changes using psychoacoustics, fMRI and EEG.

This project features a multifaceted, parallel approach in mouse and human. Each Aim will:

  1. examine auditory processing at multiple adult ages;
  2. use similar acoustic stimuli in both species, accounting for species differences in hearing, to target common mechanisms;
  3. test the effects of nicotine.

A successful outcome will promote an integrated understanding across levels, from cellular mechanisms to perception, and facilitate translation of nicotine-based therapeutic treatments to clinical populations.

nicotine for hearing improvement grant screenshot
Image source: HHS Tracking Accountability in Government Grants System (TAGGS), 5/1/2021

Public Health Relevance Statement

Nicotine enhances auditory and cognitive functions because it mimics the brain’s system for “paying attention” to important sounds amid distractions (for example, understanding speech in a noisy environment). In part, nicotine does this by activating inhibitory neurons in the auditory cortex. Since age-related hearing deficits result in part from the loss of inhibitory neurons, this project will determine, in humans and mice, whether nicotine’s effects can compensate for reduced inhibition in aging and thereby restore auditory function.

For some more background on the science and theory behind nicotine and hearing, here is a good paper from last year:

Nicotine Enhances Auditory Processing in Healthy and Normal-Hearing Young Adult Nonsmokers March 2020
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039769/

Nicotine improves auditory performance in difficult listening situations. The present results support future investigation of nicotine effects in clinical populations with auditory processing deficits or reduced cholinergic activation.

The UC Irvine project described in this post is part of the story. There is also a separate project, also at UC Irvine, titled, “Nicotinic enhancement of auditory-cognitive processing.” (Also awarded a grant worth over $600,000.)

From the project narrative section of the description:

The drug nicotine enhances auditory-cognitive function because it “hijacks” the brain’s endogenous system for directing attention to important sounds (for example, understanding speech in a noisy environment). This project seeks to determine if one kind of nicotine receptor (a2 subtype) and one kind of neuron (VIP) in two key regions of the cerebral cortex (auditory cortex and prefrontal cortex) play essential roles in nicotine’s effects. The long-term goal is to understand brain mechanisms of auditory processing and guide development of novel drug treatments for auditory-cognitive disorders.

We will be following this research and these nicotine/hearing improvement projects and posting updates as important milestones are met.

This article is an unfinished draft and a work in progress. You are accessing it early because this not-yet-public link is sent to email subscribers.

References

Exported on 05/01/2021 from the HHS Tracking Accountability in Government Grants System (TAGGS), http://taggs.hhs.gov, Project Number 1R01AG067073-01A1

DB-301: Update on Decibel Therapeutics’ cochlear hair cell regeneration program for hearing loss

An unofficial update on Decibel Therapeutics’ secretive gene therapy program to treat sensorineural hearing loss by regenerating cochlear outer hair cells…

First, the official story, followed by a big “unofficial” update on “DB-301″…

Officially:

Laurence Reid, CEO of Decibel Therapeutics, had this to say during a recent presentation at the 20th Annual Needham Virtual Healthcare Conference – from April 15, 2021:

Laurence Reid: We have an earlier stage program with respect to the cochlea. The goal is to drive differentiation of the supporting cell, through an immature hair cell, and then on particularly to either generate the outer hair cell or potentially the inner hair cell – for treating different types of patient populations with different cellular bases for their hearing loss.

Here is a slide from the presentation:

Officially, we also have some background information thanks to a recent Decibel Therapeutics, Inc SEC filing (emphasis ours):

Cochlear Hair Cell Regeneration

Age-related hearing loss and noise-induced hearing loss affect millions of people in the United States and Europe. Research has shown that the degree of hearing loss in these populations is best predicted by the amount of outer hair cell loss. We believe that restoring outer hair cells could restore hearing in these individuals. In our cochlear hair cell regeneration program, we are designing an AAV-based gene therapy that utilizes cell-selective expression of reprogramming factors to convert supporting cells into outer hair cells. We are currently conducting preclinical in vitro and in vivo rodent studies to evaluate the cell-selectivity of certain proprietary promoters and the ability of certain reprogramming factors that may drive an outer hair cell fate.

In that same filing, we learn that Decibel Therapeutics plans to announce the targets for this cochlear hair cell regeneration program in 2022. Excerpt and pipeline snapshot:

In addition, we are advancing our cochlear hair cell regeneration program to treat acquired hearing loss by regenerating cochlear outer hair cells. We plan to announce the targets for our cochlear hair cell regeneration program in 2022.

Deceibel Therapeutics 2022 cochlear hair cell regeneration program target date

However, we might not need to wait until 2022 for that update, because…

Unofficially:

Our independent research has uncovered what appear to be details related to Decibel’s “Cochlear Hair Cell Regeneration Program” (a.k.a. the gene therapy program which could potentially be given the name “DB-301”)…

“DB-301”?

That’s our unofficial code name, inferred from Decibel’s naming scheme (“AAV.RF301” or “AAV.301” + “DB” = DB-301).

From a Decibel Therapeutics corporate overview presented during Citi’s 15th Annual BioPharma Virtual Conference:

Possibly DB-301 Decibel Therapeutics

As you can see, this slide looks like a perfect match for the cochlear hair cell regeneration program. (Which is why we’re calling this an “early update” on the program.)

Confidential?

The presentation has the word “confidential” written on page 19.

However, the source of this information – a PDF document – is currently available on Decibel’s website. (It is indexed by search engines and accessible to the public. We have archived it digitally as well, for record-keeping purposes.)

But Wait There's More meme
Was the information below included in the presentation on purpose? or accidentally? Hmmm…

Intentional?

Furthermore, within this PDF – on page 19, in very, very, very tiny text – is a list of what appear to be outer hair cell candidate targets (copy+pasted):

Hdac3 Kdm4a Mtpn Htatip2 Dnmt3a Mlxip Foxo3
oxn3 Prnp Sall1 Pknox2 Klf9 Rora Six2 Trps1 Actn4 Mef2a Pdcd11 Nfkb1 Hlcs Zfp410 Banp Zbtb7b Esrra E2f3 Zfp740 Zkscan3 Creb3l1 Ighm Zfp324 Arnt Lig1 Elk3 Zbtb40 Crem Smarca2 Nfatc2 Rest Nfib Zfp608 Nfix Smad7 Mafk Adarb1 Irf6 Nacc2 Rorb Bhlhe40 Ikzf2 Jun Zfp423 Nr3c1 Tppp Cat Zfp637 Zfp777 Kmt2a Nr2f2 Zfp592 Pura Zfp365 Zbtb46 Zfp654 BC005561 Zfp516 Cic Zhx3 Rxra Zfp106 Zfp277 Thra Tmem33 Zc3h7a Srrm3 Pds5a Zbtb4 Ube2k Ctbp2 Id4 Srebf1 Nfat5 Ddit3 Sall3 Mdm2 Srebf2 Gtf2i Prdx5 Smap2 Zbtb7a Zfp618 Gata3 Irf9 Mef2d Taf1 Zfp523 Kdm2a Abcf2 Zfp398 Zfp638 Hmg20a Msi2 Nmral1 Tead1 ead2 H2afy Irx3 Ezh2 Rfxap Sox9 Tgif2 Egr4 Egr3 Npas4 Sox11 Fhl2 Prox1 Sox2 Cers2 Gm10093 Dazap1 Dnajc21 Isl1 Ran Ebf1 Atoh1 Hes6 Rpl35 Rps10 Psma6 Akr1a1 Barhl1 Smarca5 Ruvbl1 U2af1 Gtf2a2 Zfp428 Ssbp3 Zfp326 Nuak1 Pknox1 Cyb5r1 Tceal5 Msra Cers6 Zmat4 Bcl11b Npdc1 Bcl2 Ybx1 Stub1 Zmat2 Zfp667 Yeats4 Tfdp2 Hnrnpa1 Tfdp1 Rbm17 Hmgn3 Lhx3 Cers4 Ugp2 Bax Mrps25 H1fx Nap1l1 Pax2 Traf4 Mcm6 Neurod6 Rab2a Cd59a Ptcd1 Klf7 Las1l Cdk2ap1 Mycl Nono Zfp330 Insm1 Irx2 Id1 Id2 Magoh Nr2f6 Zbtb20 Diablo Gar1 Snrpb2 Rps4x Zmiz1 Hnrnpc Nr2f1 Rbpj Lsm6 Hmgb2 Tbpl1

Is this a short list of targets that Decibel is planning to choose from and announce in 2022?

Time will tell.

But, taken together, all this information leads us to believe that Decibel Therapeutics could have an earlier update for us about all these “unofficial” details (including the name “DB-301”, which is just one possibility).

References

https://wsw.com/webcast/needham107/deci/2205522

http://www.decibeltx.com/wp-content/uploads/ARO-2021_Inner-Ear-Tropism_Poster-1.pdf

https://www.sec.gov/Archives/edgar/data/1656536/000156459021016167/0001564590-21-016167.txt

http://www.decibeltx.com/wp-content/uploads/Decibel-Corp-Overview-Q320-CITI-conference.pdf

COMMENT: This article was made available to email subscribers several days early. If you want early access to updates like this one, join the email updates list. It’s free, no spam, and your information is kept private.

AOK-1 for hearing loss: a new regenerative drug from Hough Ear Institute

Hough Ear Institute is developing a new drug that uses RNA technology to regenerate inner ear hair cells and restore lost hearing.

AOK-1 siRNA therapeutic from Hough Ear Institute slide
The source of this information is a video recording of a meeting between Hough Hearing Institute CEO Dr. Richard Kopke and members of the Central Oklahoma Chapter of the Hearing Loss Association of America. The recording was uploaded to YouTube and shared with the public on April 15, 2021.

The name of the drug is AOK-1.

Unlike Hough’s first drug, NHPN-1010, AOK-1 is not a pill.

Instead, it is an injection.

And the way it works is equally different.

New: Breakthrough Number Two from Hough Crew

The Hough pill aims to restore hearing by repairing and reestablishing the connections to hair cells. It is designed to rescue or salvage “stranded” sensory cells.

This AOK-1 injection, on the other hand, aims to restore hearing by regenerating, repairing and regrowing the sensory cells themselves. Perhaps even from virtually scratch.

The dream? That AOK-1 could someday give hearing to people affected by even the most severe forms of noise-induced hearing loss.

“…like releasing a ‘parking brake’ on the regenerative process”

Hough Ear Institute CEO Dr. Richard Kopke recently shared the first details on AOK-1, including the big idea behind its mechanism.

From the video (transcribed and lightly edited for clarity and brevity):

The next technology is the one that is injected into the ear and we call it AOK-1. And it’s a regenerative therapeutic. It’s a regenerative drug and it’s an RNA technology. It’s an RNA molecule that eliminates a protein that keeps the hair cells from regenerating in the cochlea. So it’s like a parking brake on the whole regenerative process in the cochlea. When we get rid of that protein, then the hair cells can generate.

In short, AOK-1 is being developed to awaken the human body’s innate ability to repair and regrow its lost or damaged inner ear hair cells. The same way many animals, including birds, frogs, and fish, can naturally regenerate lost sensory cells and hearing. AOK-1, a small interfering RNA achives this by interfering with the protein that is responsible for keeping this regenerative power “asleep” in humans.

A “same-day” hearing restoration procedure?

Dr. Richard Kopke also explained how the drug is being designed as an outpatient “same-day” procedure. It does not require an overnight stay at the hospital. Rather, you get it and go home shortly after. The procedure involves some numbing drops for the ear drum, followed by a minimally invasive injection of thermosensitive hydrogel that contains the active drug.

This delivery method is discussed during the presentation:

AOK-1 injection delivery method photograph

Importantly, the science appears to be getting there. In vivo animal model experiments are showing lots of promise. (The research behind AOK-1, by the way, is supported by a $1.9 million Department of Defense CDMRP grant.)

AOK-1 before and after

And although AOK-1 is still in preclinical development, Dr. Richard Kopke concluded his presentation with a “hint” at the possibility of upcoming human clinical trials…

His exact words:

Currently we’re under talks and negotiations with another pharmaceutical company that would like to take this technology, license it, and bring it to the clinic. It seems to be a robust, reproducible technology that restores hearing.

The full presentation from Dr. Richard Kopke is available on YouTube: March 2021 – Hough Institute Breakthrough – Member Meeting (uploaded on April 15, 2021). The AOK-1 part of the presentation starts at the 33 minutes, 56 seconds (33:56) timestamp.

For updates on the progress of AOK-1 and its progress toward human studies, subscribe to our free email newsletter (updates).

For those of you who are eager to dive deeper into the science behind AOK-1, here are links to the original research papers:

References:

Source: Hearing Loss Association of America – Oklahoma Central Chapter. (2021, April 15). March 2021 – Hough Institute Breakthrough – Member Meeting [Video]. YouTube. https://www.youtube.com/watch?v=WCed87H92S4

Acknowledgements: Credit belongs to reddit user u/filleorange for finding and sharing the link to this informative video. (When it was first posted to reddit, the video only had a measly 4 views!)

Comments? Questions? Feedback?

Send an email to:

michael@hearinglosstreatmentreport.com

… and say hello!