Frequency Therapeutics — Hearing Loss Regeneration

I'm pretty sure it means they are quickly trying to get all of the details worked out on this program in the next 18 months, not that they are going to use any FDA accelerated Approval program.

It would be nice if they did that though.

 

I think you are making it too complicated. It will be easy to find an ICD9 code to fit anyone with measured hearing loss. I don't think there is any need to talk about "sensory lesions".

The insurance company will want to know that a treatment works. So if there is an approved treatment for hearing loss, that is a good thing. The problem will be if they decide it is not "medically necessary". For example, there may be an expensive treatment for some condition that an insurance company will cover only if you have tried a certain number of less expensive treatments and found those treatments failed. It is hard to know how they would treat "mild" hearing loss.

I'm not sure how audiologists factor into this. If we keep the topic on Frequency, this will be a drug that is injected through the eardrum by ENTs. Audiologists won't be billing insurance companies.

 

I just found this

https://www.eurekalert.org/pub_releases/2017-02/miot-dtc021717.php

 

I need to rein in my enthusiasm about the frequency therapeutics developments. It "sounds" too good to be true
Within 18 Months the first clinical trial!

 

I don't know what to think... This might be the most realistic development to give me hope.

18 months does not sound like a random number. If they had no clue, they would say something like "within the next few years".

 

If I remember correct they mention within 18 months. 18 months being worst case.

 

And then phase 1 + 2 + 3 ?

 

Most likely. But still very positive news I think.

 

"Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor. The Lgr5-expressing cells differentiate into hair cells in high yield. From a single mouse cochlea, we obtained over 11,500 hair cells, compared to less than 200 in the absence of induction. The newly generated hair cells have bundles and molecular machinery for transduction, synapse formation, and specialized hair cell activity. Targeting supporting cells capable of proliferation and cochlear hair cell replacement could lead to the discovery of hearing loss treatments".

That would mean the new hair cells also connect themselves to the nerve ?

http://www.cell.com/cell-reports/ab...m/retrieve/pii/S2211124717301365?showall=true

 

I have read before that is what happens.

 

Yes very Maybe they could already have a product on the market in 5-6 years

 

I just did one search on the internet: https://report.nih.gov/NIHfactsheets/Pdfs/HairCellRegenerationandHearingLoss(NIDCD).pdf
Quote: NIH-supported scientists found that newly formed hair
cells and nerve cells successfully reestablish
connections in an organized way, although the
reconnected nerve endings are simpler than those
generated during normal development.
This and other research will help reveal how nerve cells form
connections with newly generated hair cells.
That was 2010!

 

I will be the Debbie Downer. They can grow hair, the difficulty is making them able to work like the previous ones they are replacing... ability to transmit sound.

https://report.nih.gov/NIHfactsheets/Pdfs/HairCellRegenerationandHearingLoss(NIDCD).pdf:

To test this theory, NIH-supported scientists destroyed hair cells in a mouse inner ear. Time lapse photography showed neighboring supporting cells migrating to the hair cell region and growing hair bundles on their surfaces. Although the process did not result in restored hearing in the mice, researchers began to investigate whether experimental augmentation of the process might improve hearing loss.

Effective treatments is like finding a needle in the haystack. Maybe this one will succeed where others have failed. Only 1 in 10 treatments make it through the clinical trial process. Seeing we have had a number of failures over the years maybe we will have a success... It will be a long wait and until the trials come out, but I will be one willing to lend an ear for experimentation.

 

I didn't see that
On the positive side, researchers and Frequency Therapeutics will be hopeful or even better, discovered something.
Important enough to make them decide to publish that they will start the first clinical trial so soon.
Just regenerating hair-cells that do not improve hearing loss is obviously not their goal.

 

this article is also from 2010. i would expect progress over the last 7 years from when this report was published.

 

Yes they wouldn't say that they want to start clinical trials in humans in 18 months if they weren't able to restore hearing in mouse...
They probably tested ABR

 

Even SICHL didn't exist in 2010, it doesn't make sense talking about papers of 2010, things are progressing fast.

 

On the other hand. sometimes I feel that there is very little progress. As if there is this invisible force pushing back.

 

Science research progresses exponentially. Seven years is a loooong time. Just trust these guys, they know what they're doing.

 

Here in the states, most large ENT

Bottom line is frequency has a concept and they are going to develop it. It sounds promising. I don't think there is anything that will stop them. No invisible force. We will see what happens and it should be interesting. Keep in mind though that testing in mice doesn't always transfer well to what will happen in humans as seen by AUT00063. If all goes well, clinical trials start in 18 months and then approx 3-4 years after they will be complete with phase 3 and hopefully it is a success and we will have a treatment.

Novartis might have a treatment before then. Who knows, depending on what happens in the clinical trials. It sounds like Decibel is taking a more ground up approach by continuing to do research and figure out everything they can before trying to develop a concept for a clinical trial. 18 months is a long time though and they might have something too.

 

"We further tested the conditions using one sample of healthy human inner ear tissue isolated from a 40-year-old male patient undergoing a labyrinthectomy to access a tumor on the brain. The inner ear tissue was microdissected to remove bone, debris, and nerve tissue. The tissue was then treated identically to the mouse tissue to isolate single cells for culture. The single cells formed clonal colonies after 12 days under EFICVP6 conditions, although expansion was not as robust as that seen for neonatal cells (Figure 6Figure 6F). The colonies stained for Sox2, a known marker of inner ear progenitor cells (Figure 6Figure 6F). After 12 days of expansion, the cultures were treated with LY411575 and CHIR for 10 days to differentiate the colonies. The colonies stained positively for the hair cell marker myosin VIIa (Figure 6Figure 6G), suggesting that sensory epithelium from adult human inner ear can also give rise to hair cell progenitors."

We're almost "past" the mice stage.

 

http://news.mit.edu/2017/drug-treatment-combat-hearing-loss-0221

 

no idea why this hasn't blown up on this forum. imagine what the knowledge of these discoveries will be 5 years from now! especially if we start fast tracking regenerative medicine. with great advances comes more funding. all good things.

 

I'm in construction and build restaurants. They will have a timeline that literally gets down to the day. It's called a Gantt chart and they have processes that have been done before and they know how long it takes. So I could be building a restaurant that will be done in 56 days.

 

I'm fascinated by the credence given to press releases by people on this forum. The 18 months comes from Frequency's press releases. I'm sure it is a goal, and I hope it is met. In fact, there may be reasons (described below) to be cautiously optimistic, but they don't come from the marketing department. As an example of why I think caution is in order, consider this article from January 5, 2017 http://www.xconomy.com/boston/2017/...langer-aims-to-fight-hearing-loss-with-drugs/ where it says "Frequency hopes to enter human clinical trials in the next 18 months in patients with hearing loss, according to the spokeswoman." This is almost 2 months ago but they aren't talking about trials within 16 months now. It will be interesting to see if/when the timeline they give changes.

It's also the case that based on the paper in Cell Reports we don't know whether the hair cells are functional. They have many properties of hair cells but that has been true in other cases. In this article (http://www.livescience.com/57952-scientists-grow-hair-cells.html), Edge acknowledges this "These laboratory-grown hair cells appear to have many of the characteristics of actual inner and outer hair cells, although they might not be fully functional, Edge said."

So the cautions are 1) we don't yet know whether the hair cells are functional and additionally 2) the process is less effective for adults. From the paper "While the extent of expansion of Lgr5+ cells from adult mouse tissue was less than that from neonatal cells, the normally quiescent supporting cells from the adult mouse, rhesus, and human inner ear responded to the small-molecule cocktail used on neonatal tissue. However, additional molecules will likely be required to enhance the expansion of Lgr5+ cells from the adult cochlea."

There are, however, reasons to be (cautiously) optimistic. The paper was initially submitted on December 30, 2015. So the initial work was done in 2015. The revised paper was received on January 5, 2017. So revisions took about a year. What this means is that they have known at least some of these results for over a year and have surely been building on these results over that time. This makes it very likely that they know the answers to some of the questions we have. They may or may not be the answers that they or we would like, but they know more now than is in this paper. What will be interesting will be to see the next paper. How quickly will there be a second paper? Will they show that the hair cells are actually function? Will Frequency have the additional molecules needed to enhance the expansion of cells in the adult cochlea? Will they be able to demonstrate that injection of these molecules into a living mouse can restore noise damaged hearing? Assuming they get that far, will that work if the damage is "old"?

Additionally, based on my reading of regenerative medicine trials, assuming we get to trials (which in spite of the press releases isn't guaranteed yet) there may not need to be separate Phase 1 and Phase 2 trials. Unlike "normal" medicine where it makes sense to test for side effects in healthy volunteers, in regenerative medicine trials it doesn't make sense to regenerate things in healthy people so pure Phase 1 seem not to be done. Thus, my expectation would be that like the Genvec trial, we would see a small Phase 1/2 trial with the possibility of a separate Phase 2 or maybe even Phase 3 trial next. Another question about trials is how long they will need to be. Improvements in hearing should happen relatively quickly. The question would be how long the trials would need to be to address either safety concerns or the durability of any initial benefits.

Lastly, completely missing from the focus on "18 months" is the more immediate benefit. Assuming it is replicated by others, this approach immediately dramatically increases the number of hair cells that can be generated for research. This will speed tests of drugs, understanding of development, etc. This has the potential to be very beneficial for many labs working with hair cells. (I also don't know how Frequency's patent application(s) will affect anything.)

As an aside, it is interesting that the revised paper was received by the journal on January 5, 2017 and Frequency "went public" and announced their board of directors on, you guessed it, January 5, 2017 (http://www.frequencytx.com/news-events/pr-01-05-2017.php). On Jan 5, they wouldn't have known with certainty that the paper would be published (it wasn't accepted until the 25th), but they would have had a good idea that it would be. Who knows whether they were related but interesting timing nonetheless.

 

Thank you for this great info! wonderful to read! I had no idea. And to make things more exciting, there is another company-Decibel Therapeutics, that is working on the same concept! "The company is testing a number of potential drug candidates for drug- and noise-induced hearing loss, genetic conditions and tinnitus." So there is motivation to be the company to come out with this first!
http://medcitynews.com/2017/01/biotech-startups-hearing-loss/?rf=1