Cognosetta — Tinnitus and Hearing Disorder Therapeutics

Cognosetta

• is a drug discovery company advancing pharmaceutical therapies for tinnitus and other hearing disorders. Our focus is the discovery and development of safe and effective medications.
• At Cognosetta, we value scientific research exploring ion channels as targets for neurological diseases. We are open to industry, academic, and government partnerships to validate ion channel targets and develop drug candidates that influence ion channel function.
• Cognosetta's hearing disorder treatment pipeline now includes both small peptide and small molecule ion channel modulators.

Idea
Ion channels influence how brains cells, or neurons, shape the flow of information in the brain. Changes in ion channel function alter how neurons integrate and pass on electrochemical signals to other neurons. At Cognosetta, our medications development program is based on the idea that adjusting ion channel and neuroreceptor function can return neuronal signaling to normal, promoting healthy brain function and remedying disorders that originate in the brain.

Research
Our pre-clinical results support the utility of targeting a specific ion channel for treating hearing disorders like tinnitus and age-related hearing loss. Our pipeline now includes both small peptide and small molecule modulators of this ion channel. We have shown pre-clinical utility for ameliorating tinnitus. In other pre-clinical studies, we have shown utility in counteracting a loss of sensitivity to sounds that occurs with age.

Peptides
Using a unique screening technique, we discovered a new class of peptides that modulate ion channel function and shape brain function. Our peptides (patent pending) are bioavailable to the brain, alter neuronal signaling in auditory brain areas, and alter behavioral measures of auditory function.

Progress
Our scientists have identified a drug target and drug candidates for improving electrophysiological and behavioral measures of tinnitus and age-related hearing loss. Our ongoing research is advancing quantitative methods for evaluating the efficacy of new drug candidates that can be shared across the pre-clinical and clinical development stages. This will improve the reliability of the drug development process for hearing disorders. Our development process also supports pre-clinical models that will facilitate treatment development for military personnel who have had one or more blast exposures.

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I'm intrigued. Skeptical but intrigued.

 

I wish @Danny Boy was here to see this, I always think about him. He was such a positive contributor to the tinnitus community and spoke about ion channels.

A brief look behind the science that this early stage biotech is focused on.

 

Has anyone got in touch with them to ask when their clinical trial will start?

 

They don’t even have a product to test for clinical trials... yet... if ever.

 

At least they aren’t rushing it. Drugs seem increasingly dangerous these days.

 

Thanks for sending this email and getting this info. I came here hoping somebody knew more about this company. I was hoping they were a little further along than this. Hopefully they have enough money to keep the lights on until they figure out something that helps.

 

Patent granted
February 1, 2019
A patent for the small peptides discovered and developed by Cognosetta, Inc scientists has been fully granted.

SBIR Grant Awarded
December, 2019
Cognosetta, Inc is excited to receive a SBIR Grant from the NIH to complete dosing and safety trials for our Tinnitus pipeline candidates. We can't wait to share our results later in the year!

 

From this website : https://projectreporter.nih.gov/project_info_details.cfm?aid=9907138&icde=48273554

Abstract Text:
Project Summary
Tinnitus or “ringing in the ears” is a hearing disorder that disproportionately impacts those who are or have served in the military. There is currently no effective cure for tinnitus. Patients with tinnitus exhibit broad changes in brain activity in the auditory system and elsewhere. One of the fundamental characteristics of tinnitus is a dysregulation in the excitatory/inhibitory balance in the central auditory system (CAS) leading to neuronal hyperexcitability and synchrony. The large conductance calcium-activated potassium (BK) channel is implicated in other neuronal excitability disorders like temporal lobe epilepsy, tonic-clonic seizures and alcohol withdrawal seizures. Gated by both voltage and intracellular calcium, and expressed throughout the peripheral and central auditory system, the BK channel is able to modulate auditory neuronal signaling across a wide variety of conditions. Recently, Lobarinas et al. found that two BK channel openers, Maxipost and its enantiomer, reduced behavioral evidence of salicylate-induced tinnitus in rats. Though Maxipost was originally developed as a BK channel opener, in fact it is a more potent KCNQ channel opener. Nonetheless, these findings provided the impetus for our preliminary studies showing that BMS-191011, a more specific BK channel opener, reduces behavioral manifestations of tinnitus in two mouse models. Consistent with a mechanistic aim of counteracting hyperactivity in the CAS, our preliminary data and other’s shows that BK channel openers reduce neuronal activity in the auditory midbrain. The overall aim of the proposed studies is to test whether treatment with a class of BK channel openers, exemplified by BMS-191011, can reduce behavioral and neurophysiological manifestations of chronic tinnitus. Behavioral assays will probe whether treatment with the BK channel opener modifies responses that can be linked to CAS function. Both invasive and non-invasive neurophysiological recordings in vivo will characterize treatment effects on neural correlates of tinnitus in the CAS to 1) provide cross-methodological confirmation for the behavioral effects, 2) facilitate preclinical target validation and engagement studies, and 3) allow translation to clinically-measurable markers of tinnitus. The studies will employ a mouse model of acoustic trauma-induced tinnitus that matches the etiology of a substantial portion of the patient population. The use of mice will enable a longitudinal study design in which treatment begins ~2-3 months after acoustic trauma. Many mammals preclude long duration studies or higher usage rates, but the CBA/CaJ mouse is both affordable and now considered a reliable model of tinnitus following noise trauma. Together, the proposed preclinical studies will explore whether administration of a class of BK channel openers exemplified by BMS-191011 is a valid strategy to counteract maladaptive CAS function underlying stable tinnitus. This therapeutic approach clinically would allow a lapse in time following noise trauma before treatment onset, in line with the practical needs of at-risk members of the Armed Forces who may develop tinnitus while deployed, and the many patients who already have acoustic trauma-related tinnitus.

Public Health Relevance Statement:
Project Narrative
Ion channels regulate neural processing; and, changes in ion channel function can underlie central nervous system disorders. tinnitus or “ringing in the ears”, which is characterized by hyperexcitability in the central auditory system, may be relieved by modulating the function of specific ion channels. This project will explore whether a specific class of potassium channel modulators can reduce the neural and behavioral manifestations of chronic tinnitus.

 

Cognosetta update: CS0022 (earlier BMS-191011)



from cognosetta.com

Isn't it interesting that CS0022 seems to be mentioned both for tinnitus and Fragile X Syndrome/Autism? Is there a neurological relation between tinnitus and autism?

Luisa Scott, Ph.D., from Cognosetta, has submitted a poster presentation to the 44th Annual ARO MidWinter Virtual Meeting:



Following pasted from the poster, cs0022-chronic-tinnitus-bk-channel.pdf:

Background:
Subjective tinnitus is an audiological and neurological condition that gives rise to a phantom perception of sound. The condition disproportionately impacts individuals with risky occupational or avocational noise exposure. Patients and animal models of tinnitus exhibit altered central auditory system (CAS) neural activity that is presumed to support the tinnitus percept. Broadly, these changes can be characterized by a dysregulation in the balance of excitation and inhibition that leads to neuronal hyperexcitability and synchrony. The large conductance calcium-activated potassium (BK) channel regulates neural excitability in the CAS and other brain regions. Our recent work suggests that systemic administration of a class of BK channel openers reduces salicylate-induced tinnitus in mice through action in the CAS. The main objective of the current study is to determine whether a similar low-exposure treatment also reduces behavioral and neural manifestations of tinnitus in a chronic tinnitus model induced by noise exposure.

Methods:
Auditory brainstem response (ABR) thresholds and acoustic startle behavior were assessed in young adult CBA mice before and after acoustic trauma. For acoustic trauma, awake mice were placed in a small, sound transparent cage, and then exposed for 1 hour via free field to a 113 dB SPL, 1 kHz wide band noise centered at 16 kHz. Ten weeks after damaging noise exposure, mice began systemic treatment with a BK channel opener, CS0022. Gap-prepulse inhibition of the acoustic startle reflex (GPIAS) tracked the development of tinnitus and subsequent effects of treatment. A novel machine learning algorithm and computational analysis method was used to determine which mice displayed tinnitus from the GPIAS protocol.

Results:
The acoustic trauma procedure caused limited permanent ABR threshold shifts, ranging from none to moderate (~50 dB) in the high frequencies above 16 kHz. Mice were selected for preliminary analysis if they exhibited minimal permanent hearing loss (< 10 dB) and GPIAS evidence of tinnitus at 16 or 32 kHz after acoustic trauma. Six out of the six selected mice showed less suppressed pre-pulse inhibition for the selected tinnitus frequencies following systemic treatment with a BK channel opener. In contrast, treatment did not influence acoustic startle amplitude functions. Pharmacokinetics studies confirmed low exposure in brain. As expected, improved startle selection via machine learning-enhanced computational analysis increased the power and accuracy for identifying tinnitus and treatment effects.

Conclusions:
Ongoing neurophysiological and alternate behavioral measures continue to probe treatment outcomes in this model of acoustic trauma-induced chronic tinnitus. Thus far, preliminary outcomes support the idea that treatment with BK channel openers such as the one used in the current study may reduce evidence of tinnitus. There is currently no effective cure for chronic tinnitus, increasing the urgency for studies exploring the utility of promising drug candidates.

 

$2.5B market in USA and Europe?!

Is that it?

Where did they get the figures from? I was under the impression tinnitus is more common than hearing loss.

 

What about India and China? $2.5B sounds low.

 

Nah man. Tinnitus is a side effect or residual from hearing loss. Many will argue otherwise but they have hearing loss too. There are a select few with tinnitus who have normal audiograms from 125 Hz to 16 kHz but that is extremely rare.

 

They do state that this number is for moderate to severe tinnitus sufferers so they've probably narrowed it down to a small subset of the tinnitus population. If they were to take into account all severities it'd be way, way higher.

 

It makes me happy to know that within 10 years there will be many drugs on the market for hearing loss. No man, woman, or especially child should have to live with this currently permanent disability.

 

Good share, @SallyM!

 

What happened to Cognosetta? Their website has been offline for months... Does anyone have further information about them?

 

This article is from August 2022. Animal study using BK channel openers to reduce tinnitus in rats. It's the same author as in the above papers in this thread.

Small molecule modulation of the large-conductance calcium-activated potassium channel suppresses salicylate-induced tinnitus in mice

Findings:

• Reduced tinnitus
• Did not reduce hyperacusis

 

What does this mean for the company "Cognosetta" and their product?

 

@HopeForSilence, I'm not sure. If they are not pursuing human trials, it means nothing. It's just a proof of concept in animals, which may or may not translate to humans.

I noticed Luisa Scott, PhD, was the lead author on the paper and she is involved with Cognosetta.

We never know what will translate from animal to human. Rats are not as reliable as guinea pigs when it comes to hearing pathways being similar to humans. All the work from the Shore Lab started with guinea pigs.