Cilcare's CIL001 Targets Cochlear Synaptopathy — An American/French Collaboration

[Muggumbo]

What email address did you use to make contact?

I used info@cilcare.com as well.

 

[Joeseph Stope]

Some news:

→ Cilcare wins prestigious Hearing Technology Innovator Award for CIL001

Hey, am I missing something? I thought that phase one trials were meant to prove safety and phase two trials to demonstrate effectiveness. Where have I gone wrong, or what's the reason for all this optimism?

 

[StoneInFocus]

CIL004 looks promising, too, but I haven't been able to find any information about it.

 

[Joeseph Stope]

It would be nice to join the "optimism fest" and "hope bash." It even makes some sense that fixing the synapses could alleviate tinnitus. After all, the synapses are like connecting cables that link the hearing nerve on one side and the hair cells on the other.

If this approach works, plausible explanations could be constructed to explain why, in past attempts, one patient benefits from Therapy A while another benefits from Therapy B, and so on. It's like a mechanic trying to fix a motor in the dark.

Well, roll on the tests and the results in 2025. I'll believe it when I see it.

 

[Justin Mills]

I'm not sure how this compares to OTO-413 or the work by Frequency Therapeutics. Hopefully, Cilcare's molecule will be the one that finally works, and with just one injection! How many years will this take?

 

[Justin Mills]

"What we do is magical, to regrow auditory nerve fibers towards the hair cell"

 

[Kam75]

"What we do is magical, to regrow auditory nerve fibers towards the hair cell"

I'm glad I can hear a video on TInnitus Talk in my mother tongue!

 

[Nick47]

Hmm. An advertisement for Cilcare. There are lots of magnified images, smiling faces, and people in lab coats.

 

[Fields]

Hmm. An advertisement for Cilcare. There are lots of magnified images, smiling faces, and people in lab coats.

Maybe they are feeling optimistic and trying to get their name out there. They have already signed a deal with Shionogi, which included an upfront payment of 15 million USD. Depending on the milestones they achieve, the contract could be worth up to 400 million USD.

On the other hand, someone in marketing might have just thought, "Let's put out a video for our 10-year anniversary."

There is not really a clear call to action, it just ends with a message thanking viewers for their continued confidence.

 

[ColinUK]

Since Frequency Therapeutics' failure, I've stopped getting excited about things like this, but I truly wish them the best and hope they find the magic.

To achieve that, they'll need to generate interest and secure investment, so I'm all for it. That said, I just hope it doesn't involve news pieces showcasing patients miraculously cured, only for the clinical trial to fail shortly after.

It would be amazing if the French figured it out. A quick train ride to get new ears? That would work for me!

 

[Fields]

Since Frequency Therapeutics' failure, I've stopped getting excited about things like this, but I truly wish them the best and hope they find the magic.

To achieve that, they'll need to generate interest and secure investment, so I'm all for it. That said, I just hope it doesn't involve news pieces showcasing patients miraculously cured, only for the clinical trial to fail shortly after.

It would be amazing if the French figured it out. A quick train ride to get new ears? That would work for me!

That would, indeed, be pretty great. From St Pancras to Paris in 2 hours or so?

 

[Eloy79]

Luckily, the arrow of time only moves in one direction. I think dwelling too much on possible treatments that failed in the past sometimes becomes a trick of the mind. It's a very human thing, but it only brings pessimism to oneself.

 

[Justin Mills]

There is literally nothing else out there as a potential cure for tinnitus except Cilcare's treatments. Frequency Therapeutics, Otonomy, and Pipeline Therapeutics have all failed. However, some of their approaches didn't make much sense. For example, Pipeline specifically excluded people with tinnitus from their trials for a regenerative drug. This exclusion doesn't make sense because individuals with more severe cochlear synaptopathy are often the same ones who experience worse tinnitus and hyperacusis.

Cilcare seems to have a better understanding of this connection, as they've stated that their drug targets both synaptopathy and tinnitus. Regardless, as I mentioned, there's currently nothing else available with regenerative potential.

I recall someone on this forum saying that Dr. Stéphane F. Maison, PhD, mentioned he would try to get them into the Cilcare trials. I doubt Dr. Maison would be paying attention to Cilcare's trials if they didn't show promise. The only downside is that it will take years before we know if it truly works.

 

[IYIiKe]

There is literally nothing else out there as a potential cure for tinnitus except Cilcare's treatments. Frequency Therapeutics, Otonomy, and Pipeline Therapeutics have all failed. However, some of their approaches didn't make much sense. For example, Pipeline specifically excluded people with tinnitus from their trials for a regenerative drug. This exclusion doesn't make sense because individuals with more severe cochlear synaptopathy are often the same ones who experience worse tinnitus and hyperacusis.

Cilcare seems to have a better understanding of this connection, as they've stated that their drug targets both synaptopathy and tinnitus. Regardless, as I mentioned, there's currently nothing else available with regenerative potential.

I recall someone on this forum saying that Dr. Stéphane F. Maison, PhD, mentioned he would try to get them into the Cilcare trials. I doubt Dr. Maison would be paying attention to Cilcare's trials if they didn't show promise. The only downside is that it will take years before we know if it truly works.

Have you considered he's paying attention because he's literally from France and that is where Cilcare is?

 

[Nick47]

as I mentioned, there's currently nothing else available with regenerative potential.

@Justin Mills, does Rincell-1 have no regenerative potential?

 

[Alberte]

I seems that the Japanese company Shionogi has taken charge of the development of Cilcare CL001.

Option Agreement with Cilcare for Development Compounds Addressing Hearing Loss

www.shionogi.com

 

[lolkas]

There is literally nothing else out there as a potential cure for tinnitus except Cilcare's treatments. Frequency Therapeutics, Otonomy, and Pipeline Therapeutics have all failed. However, some of their approaches didn't make much sense. For example, Pipeline specifically excluded people with tinnitus from their trials for a regenerative drug. This exclusion doesn't make sense because individuals with more severe cochlear synaptopathy are often the same ones who experience worse tinnitus and hyperacusis.

Cilcare seems to have a better understanding of this connection, as they've stated that their drug targets both synaptopathy and tinnitus. Regardless, as I mentioned, there's currently nothing else available with regenerative potential.

I recall someone on this forum saying that Dr. Stéphane F. Maison, PhD, mentioned he would try to get them into the Cilcare trials. I doubt Dr. Maison would be paying attention to Cilcare's trials if they didn't show promise. The only downside is that it will take years before we know if it truly works.

I have been following regenerative approaches since 2016 and have observed many developments. The same applies to Dr. Susan Shore and other approaches specifically for tinnitus management.

Past hearing regeneration efforts discussed on Tinnitus Talk, like Frequency Therapeutics and others, focused on singular objectives, primarily targeting either IHC and OHC (inner and outer hair cells) or synapses.

For example, Frequency Therapeutics' approach focused on regenerating IHC and OHC by proliferating supporting cells, but it did not address synapse regeneration. Additionally, the regenerated IHC and OHC sometimes grew irregularly, although I am unsure how significant that issue is.

To illustrate, you can compare IHC and OHC to car parking sensors. If your parking sensor malfunctions, your car's computer shows a warning. Similarly, if the wiring harness is cut or unplugged, the computer generates an alert. I believe something similar happens with hearing and tinnitus. When the brain senses it has lost connection to the "parking sensors" (IHC and OHC), it cannot determine the exact cause but generates a warning signal—tinnitus.

If we ever aim to address the root causes of most hearing loss and tinnitus, such as SSHL (sudden sensorineural hearing loss), SNHL (sensorineural hearing loss), NIHL (noise induced hearing loss), or ototoxicity from drugs, we must repair both IHC and OHC as well as synapses.

I recall seeing a theory suggesting that tinnitus could often arise more from the loss of synapses than from IHC and OHC damage.

If this company only focuses on repairing synapses, it might reconnect missing synapses to still-functioning IHC and OHC, which could bring some benefits. However, in my opinion, it would not fully resolve the problem. That said, if someone loses synapses while their IHC and OHC remain somewhat functional, this drug, if effective, could have practical benefits.

Another researcher worth mentioning is Dr. Zheng Yi Chen, who is rarely discussed. As I understand it, his team's research does not focus solely on IHC and OHC repair or synapse repair. It addresses both.

I watched a 2023 interview where Dr. Chen discussed his research and mentioned two areas of focus:

1. Genetic hearing loss (people born deaf)
   
   His team identified specific genes that were not functioning properly and conducted a small proof of concept trial in Shanghai (late 2023 to early 2024) involving six children born deaf. Remarkably, five out of the six regained hearing. This differs from typical hearing loss because individuals born deaf lack functional IHC and OHC, which prevents them from generating electrical signals in response to sound vibrations. This progress is groundbreaking and had never been achieved before.
   
   
2. Acquired hearing loss (e.g., SNHL, NIHL, ototoxicity)
   
   For acquired hearing loss, Dr. Chen's approach involves gene therapy. He described it as "turning the clock backward" in the inner ear by tricking it into a developmental stage. This process activates dormant genes and enables the ear to rebuild missing structures based on the DNA blueprint.

His team conducted proof-of-concept tests on lab mice and wild mice. In his words, "it worked beautifully." If I remember correctly, the repair cycle took about four to six weeks, similar to the speed at which birds regenerate their hearing.

Despite this success, Dr. Chen mentioned challenges they were addressing, such as the delivery method. For example, precise inner ear injections currently require cutting behind the ear. Additionally, while the viral vector used for the tests was effective, it was not ideal. They are already developing a better and safer viral vector for future use.

Apologies for the lengthy post, but I wanted to outline everything clearly. This company may be the only one nearing clinical trials in the short term, but other promising advancements could be on the horizon.

 

[Justin Mills]

Synapses are the most important to treat first because they are the most vulnerable. Before hair cells are damaged, it's the synapses that are destroyed. Regenerating the synapses would restore all the sound information received by the hair cells, improving hearing clarity and the input of sound. This, in turn, would allow central gain to decrease, potentially reducing or even eliminating tinnitus.

Regenerating synapses would also address hyperacusis, which arises from synapse damage. I struggle with both issues—it's painful even to hear myself speak much of the time. High-pitched sounds cause me pain, and I also experience distortion simultaneously. While there is some hair cell loss, it's proportionally much less than the loss of synapses. There's no doubt that regenerating synapses would dramatically improve and restore quality of life.

I didn't know about Dr. Zheng. What he's working on is incredible, though it might take quite a while to become clinically available.

 

[ccpjc]

I have been following regenerative approaches since 2016 and have observed many developments. The same applies to Dr. Susan Shore and other approaches specifically for tinnitus management.

Past hearing regeneration efforts discussed on Tinnitus Talk, like Frequency Therapeutics and others, focused on singular objectives, primarily targeting either IHC and OHC (inner and outer hair cells) or synapses.

For example, Frequency Therapeutics' approach focused on regenerating IHC and OHC by proliferating supporting cells, but it did not address synapse regeneration. Additionally, the regenerated IHC and OHC sometimes grew irregularly, although I am unsure how significant that issue is.

To illustrate, you can compare IHC and OHC to car parking sensors. If your parking sensor malfunctions, your car's computer shows a warning. Similarly, if the wiring harness is cut or unplugged, the computer generates an alert. I believe something similar happens with hearing and tinnitus. When the brain senses it has lost connection to the "parking sensors" (IHC and OHC), it cannot determine the exact cause but generates a warning signal—tinnitus.

If we ever aim to address the root causes of most hearing loss and tinnitus, such as SSHL (sudden sensorineural hearing loss), SNHL (sensorineural hearing loss), NIHL (noise induced hearing loss), or ototoxicity from drugs, we must repair both IHC and OHC as well as synapses.

I recall seeing a theory suggesting that tinnitus could often arise more from the loss of synapses than from IHC and OHC damage.

If this company only focuses on repairing synapses, it might reconnect missing synapses to still-functioning IHC and OHC, which could bring some benefits. However, in my opinion, it would not fully resolve the problem. That said, if someone loses synapses while their IHC and OHC remain somewhat functional, this drug, if effective, could have practical benefits.

Another researcher worth mentioning is Dr. Zheng Yi Chen, who is rarely discussed. As I understand it, his team's research does not focus solely on IHC and OHC repair or synapse repair. It addresses both.

I watched a 2023 interview where Dr. Chen discussed his research and mentioned two areas of focus:

1. Genetic hearing loss (people born deaf)
   
   His team identified specific genes that were not functioning properly and conducted a small proof of concept trial in Shanghai (late 2023 to early 2024) involving six children born deaf. Remarkably, five out of the six regained hearing. This differs from typical hearing loss because individuals born deaf lack functional IHC and OHC, which prevents them from generating electrical signals in response to sound vibrations. This progress is groundbreaking and had never been achieved before.
   
   
2. Acquired hearing loss (e.g., SNHL, NIHL, ototoxicity)
   
   For acquired hearing loss, Dr. Chen's approach involves gene therapy. He described it as "turning the clock backward" in the inner ear by tricking it into a developmental stage. This process activates dormant genes and enables the ear to rebuild missing structures based on the DNA blueprint.

His team conducted proof-of-concept tests on lab mice and wild mice. In his words, "it worked beautifully." If I remember correctly, the repair cycle took about four to six weeks, similar to the speed at which birds regenerate their hearing.

Despite this success, Dr. Chen mentioned challenges they were addressing, such as the delivery method. For example, precise inner ear injections currently require cutting behind the ear. Additionally, while the viral vector used for the tests was effective, it was not ideal. They are already developing a better and safer viral vector for future use.

Apologies for the lengthy post, but I wanted to outline everything clearly. This company may be the only one nearing clinical trials in the short term, but other promising advancements could be on the horizon.

Imagine if companies could bring a product to market and continue improving its administration later. I imagine a lineup of people would fill the streets, even if the current delivery method is less than ideal. The companies could then use the profits to refine the next version of the product.

 

[withintention]

Is this the doctor?

 

[Mdi]

Synapses are the most important to treat first because they are the most vulnerable. Before hair cells are damaged, it's the synapses that are destroyed. Regenerating the synapses would restore all the sound information received by the hair cells, improving hearing clarity and the input of sound. This, in turn, would allow central gain to decrease, potentially reducing or even eliminating tinnitus.

Regenerating synapses would also address hyperacusis, which arises from synapse damage. I struggle with both issues—it's painful even to hear myself speak much of the time. High-pitched sounds cause me pain, and I also experience distortion simultaneously. While there is some hair cell loss, it's proportionally much less than the loss of synapses. There's no doubt that regenerating synapses would dramatically improve and restore quality of life.

I didn't know about Dr. Zheng. What he's working on is incredible, though it might take quite a while to become clinically available.

Dr. Zheng-Yi is not only working on synapse restoration but also on the complete restoration of the cochlea, using your DNA as a blueprint. Essentially, this process aims to reset it to its original "factory settings."

 

[Ferna]

Is this in Phase 2? I just checked their pipeline:

 

[Justin Mills]

Dr. Zheng-Yi is not only working on synapse restoration but also on the complete restoration of the cochlea, using your DNA as a blueprint. Essentially, this process aims to reset it to its original "factory settings."

Yes, it's wonderful, and his other treatment has already worked on five children born deaf. However, it will likely take many years before it becomes clinically available.