Inner Ear Hair Cell Regeneration — Maybe We Can Know More

I think this is a great thing. It's should provide a lot of relief maybe a cure for my T. Though because this hasn't created new neuron I would probably revert to T over the course of life and more neuron death.

 

Great find!! I definitely something i'd like to participate in.

 

Another paper using Anc80L65. They show that injection through the semicircular canal in adult mice can reach essentially all areas of the cochlea - inner and outer hair cells along the entire cochlea as well as supporting cells. There was also no measurable damage to hearing from the procedure. Paper is at http://www.nature.com/articles/srep45524

This is something of a follow-on to one of the Anc80L65 papers published a couple of months ago (http://www.nature.com/nbt/journal/v35/n3/full/nbt.3781.html).

Key differences seem to be

1) the use of adult rather than newborn mice (this is important)
2) different injection approach
3) more general exploration of areas reached by virus
4) more detailed safety analysis - they are particularly concerned about potential damage to the cochlea when doing surgery on adults

With 3 papers in two months on Anc80L65, this will be something to keep an eye on.

 

A bit more followup.

First, from http://www.nature.com/articles/srep45524, "the work in the paper was partially supported by Decibel Therapeutics."

Second, from http://www.nature.com/nbt/journal/v35/n3/full/nbt.3801.html, "The Anc80L65 vector is patented by L.H.V., patent #WO/2015/054653 – “Methods of predicting ancestral virus sequence and uses thereof.”" I didn't find a granted patent (though I am not a patent attorney), but I did find an application: http://appft.uspto.gov/netacgi/nph-...=Vandenberghe&OS=Vandenberghe&RS=Vandenberghe

Third, from http://www.nature.com/nbt/journal/v35/n3/full/nbt.3781.html, "L.H.V., K.M.S., and J.R.H. have filed a patent on the use of Anc80L65 in the cochlea." I didn't see an application for this, but it is possible that it takes time to show up in the on-line data base - it hasn't been "published" yet.

Fourth, from http://www.nature.com/articles/srep45524, "L.H.V. has filed a patent application on the use of Anc80 in the cochlea." Again, I didn't find the patent application, but this is presumably his application with Stankovic, and Holt. (Vandenberghe does have a patent using AAVs the eye http://patft.uspto.gov/netacgi/nph-...=Vandenberghe&OS=Vandenberghe&RS=Vandenberghe. He's actually published quite a lot on vision, so he seems to be moving to the ear now.)

It's clear that Vandenberghe is the virus guy. He's now worked with senior authors Charles Liberman, Konstantina Stankovic, Jeffrey Holt, and Gwenaëlle S Géléoc. Together this is a serious group. It also will be interesting to see whether Decibel will license Anc80L65.

 

Hey guys: the tinnitus was definitely from losing all my hearing and like i might have said in the past, the tinnitus started like 6 months after being deafened in the accident. When i went to the ENT way back and told them about the crazy noises they said, "your hearing might be trying to come back!" so i thought to myself, Yeah oh please let that be. But eventually i found out myself what the noises were. I didnt even know they had a name!! Imagine having 5-10 different noises in your head at once and not being able to hear anything except the crazy noises in your head. Thats what i endured for about 8 years till i had the cochlear implant device implanted. I drank a lot. I was near suicide and all that jazz. Doctors lied to me. Maybe they didnt want to tell me what was going on with my ears and brain. Who knows. Not much was known about tinnitus back then in the early '80's.
But i have hung in there all these years and my lil boy is 2 1/2 years old now and what a joy he is. So, i have to fight the good fight and hope and pray something is developed to quiet the noises. Thanks for encouraging words guys.

 

I imagine it must have been hell. Props to you for hanging in there.
Did the CI make any difference to your T?

How is your hearing with the CI now? How does it compare with your original (natural) hearing?

 

Perhaps there is more information regarding cochlear implants. After all a cochlear implant needs these neurons to function.

 

For those that know more I read somewhere a Chinese clinic is planning for viral introduction into the synapses of the NT-3 growth factor. Does that make sense? Are we at the stage were humans have designed a virus like AAV to contain the NT-3 growth factor. Have we been able to design a virus with will only target nerve cells? Are there other planned clinic trials using this method.

 

Where did you read this? It's not really possible to evaluate any of this without seeing the original.

I don't believe there is anything in the published literature. My guess is this is something Decibel is or will be working on.

No, not to my knowledge, but if you look a few posts up, I posted a link to a brand new article that discusses the ability of Anc80L65 to reach spiral ganglion neurons. They specifically mention the possible application of NT-3 as a motivation for the work.

I know of no trials for NT-3 regardless of method of application. Perhaps you can provide information on this Chinese trial.

 

A little historical perspective. This claim from 2014 was on some very basic science and not that many products available. While there is a ton available currently it seem like there is more companies competing with pipeline products. Almost to the stage of improvement of hearing loss which will be followed by enhancing product efficency. 2024 for a deafness cure maybe accurate and a tinnitus cure for 90% of people will happen earlier than that.

A Cure for Hearing Loss and Tinnitus Is...

 

https://www.actiononhearingloss.org...treatments-for-hearing-loss-and-tinnitus.aspx

Explains the process of why it takes so long to develop cures for hearing loss and tinnitus.

 

@RB2014 is this always the timeline or do some phases get shorten if efficacy is shown. For people on this site I could see a bunch being able to get into a phase 3 for frequency or decibel if they make it that far. Especially decibel because nerve repair/growth isn't as sexy and the general public might not connect it as much with better hearing

 

I am not an expert on this process, but I don't see any of the timelines getting shortened. There is a fast track process for the clinical trials that the fda has, that I have read about, but I don't think it would apply in this case. If you look at Novartis I think their phase 2 trial was even extended to 2019 instead of 2017. Even if efficacy is shown, they still need to evaluate the data especially if different dosages are administered and maybe even look at the different causes of the hearing loss. There could also be long term effects that don't show up immediately. I don't see any of clinical studies getting shortened.

 

If I remember correctly, the FDA granted Auris Medical the fast-track thingy for AM-101 (though none of the users of TT who volunteered got any benefit).

 

Yea I think it really depends how well it work and if there are people will major setback. If one of these company has good success early in Phase 1 and Phase 2 and no patient has extreme reactions then you can bet the FDA will relent to the public pressure to accelerate the phasing schedule.

 

This is not how clinical trials are run.

 

https://www.sciencedaily.com/releases/2017/02/170221120810.htm

Has anyone posted this yet? These scientists were able to use stem cells to regrow the hairs in mice. They created like 11,500 hairs! They say clinical trials are 18 months away. Frequency therapeutics is the company name I think.

 

Several times.

 

A new paper out of Yehoash Raphael's lab that demonstrates the challenges of transplanting stem cells into the inner ear and having them survive: http://www.nature.com/articles/srep46058

 

How's the hearing through that?

 

So stem cells typically do not survive because of the high potassium concentration.
Does a viral vector survive in this environment?

 

That is my understanding. They do survive in the perilymph but do not migrate to the auditory epithelium.

As far as I can tell, the viruses do not interact with the endolymph. They are injected through the RWM or oval windows (or diffuse across the RWM) into the perilymph. However, unlike the stem cells which do not appear to migrate to the auditory epithelium (at least in large numbers), the virus migrates throughout the inner ear. Thus, it is able to transduce OHC, IHC, SG neurons, etc.

 

I'm of a mixed mind on this. I get that this is a amazing leap forward in terms of hearing restoration but using up your supporting cells in this procedure is risky especially you don't have a lot of hearing loss. My question is if a newly grown hair doesn't get connected up does it die.

Would a safer option be to reestablish a large number of synaptic connections to your existing hair cells and by doing so get rid of your T. Then you could wait until an optimized Frequency process comes out. But it seems like Decibel and neuro stem cell procedures may be years behind Frequency. Which is weird because multiple sources have said neuron regrowth is easier than regrowing stem cells.

Would this Frequency procedure use up the supporting stem cells? Do hair cells die if they don't recieve synaptic connections within a few weeks or do they survive and wait for that connection?

 

No. Read the paper.

 

I didn't.

From http://www.nature.com/articles/srep46058

"Following delivery of cells into the scala tympani, a fluid-filled lumen adjacent to the cochlear duct epithelium, transplanted cells can survive but remain in the perilymph in scala tympani and do not reach the auditory epithelium where they need to reside to transduce sound efficiently. Consequently, it is necessary to inject the cells directly into the scala media, the fluid-filled lumen within the cochlear duct epithelium. However, the high concentration of potassium of the endolymph11 in scala media quickly kills the transplanted cells"

See also http://www.cochlea.eu/en/cochlea/cochlear-fluids