Frequency Therapeutics — Hearing Loss Regeneration

what at we are still waiting for the result from phase II

 

I Am not sure what this means, but phase 2 hasn't even started yet.

 

They partnered with US army amongst others, so I hope this indeed is true.

I think I would compare it with the invention of the combustion engine; instead of focussing on cars, you see if you can apply the technology to bicycles, trains, generators and airplanes. I hope that indeed, the platform they've discovered just works and opens up a whole new era with regenerative medicine. But get the cars working first, then look at the rest.

 

Why then the FREQUENCY Therapeutics? My take is that they started out as a hearing loss company, secured some funding, and are now expanding to apply their technology to other areas. One can only hope that the technology so promising that they want to secure patents on other applications to it before their competitors do!

 

If their first attempt fails, their entire approach fails, PCA fails so i assume they are not just betting on multiple horses!

 

Has there been any official statements from Frequency regarding vestibular disorders? If the treatment is able to regenerate hearing cells, then by definition it should help the vestibular system heal. This should translate to the easing of related symptoms for us that suffer.

 

I don't know about announcements, but just considering it logically - yes, the same drug may work, but they'd need a whole new method of delivery. The vestibular system is even less accessible than the cochlea; getting the drug in there would need some research and possibly invasive surgery from what I know.

 

https://www.businesswire.com/news/h...eutics-Lead-Featured-Session-American-Academy

"@frequencytx will lead a Featured Session at #aaaconf18 this Friday where they'll discuss #regenerativemedicine advances for sensorineural #hearingloss"

 

Cool!

I do wonder though... “triggering cells to start multiplying...”

Isn’t that like begging for cancer?

I sure hope they can also stop them

 

Um your skin cells divide and multiple every day on your body.

 

Hi everybody,

Newbie here. I joined TT a few years ago but never posted - i think. at least i dont remember posting. so this is ostensibly my first post.

my T is noise exposure induced. i have had it for over 20 years, with intermittent spikes over the years from further exposure. i'm a musician.

been reading this thread and researching Frequency Therapeutics online. looks really promising. super excited about the prospects. and they got it to Phase I roughly a year ahead of sched. pretty cool. there must be a race to get something to market like people have been saying on this thread.

was wondering if anyone knows how to be a part of the Phase II trials? i live in the US and i believe its a US-based company. so it might be easy-ish for me to at least be condsidered (?)

anyway thx for reading and i'm hoping everyone has a good day today!

 

yeah i think their primary technology is triggering stem cells to create new cells. they want to introduce the tech into several fields.

 

yes we all multiplied from a single cell. cell growth is normal. that is not an issue at all.

 

Curious what has been discussed..

 

May be we can read or watch it somewhere?

 

If I understand well the mammals had a recovery of about 10db after 5 weeks? (Slide 80)

 

And near normal after 8 weeks!

 

And the brain will respond accordingly and T and H will wash away, making its host happy again

 

If your talking slide 14; tmk unfortunately that refers to birds. If I recall well they were treated with ab.

Edit: Kanamycin, http://www.pnas.org/content/94/25/14206

Perhaps one of the more advanced scientist on this forum can eloborate whether we can learn something new from this presentation?

 

Yes, please. I don't want to be the purveyor of false information. It is hopeful information regardless! Thank you for posting the slides @Samir! They are an excellent read and easy enough to understand. I will be pointing any forum posters asking the usual questions to your post as well as those who have given up hope.

 

Hi, I don't understand the audiogram of the slide 14. What I understand is that hearing become worse after injection (wich is not logical).

They also speak about hearing "near" to normal. But normal is between 0 and 20 db, no ?

 

This is to show hearing restauration in birds. They inject ab with ototoxic effect, affecting especially hf. The bird is able to regenerate hearing afterwards.

 

Ok, thanks for explaining it to me !

So hearing between 10 and 15 is not considered as "normal" ?
I always believed that hearing was normal between 0 and 20 db, but I may be wrong...

 

Do we need to feel excited about the presentations or is it just a great summary of all we already knew ?

tks

 

In my mind, it's confirmation of what we'e all been talking about assembled and explained in one set of slides.

 

Agree. I´m afraid all talk in this tread, until information from phase II exists, is just masturbation!
Still, I understand the involvement. This is, by far, the most interesting thing happening.

 

I cant even begin to describe how much I hope they succeed with this or at least find answers on how to succeed.

 

Regarding Frequency, all that is new is the information in slides 79-80. We already knew informally that there was some hearing recovery; we now have a sense of how much, though a lot remains unknown to us.

Since the treatment was CHIR and VPA without a gamma secretase inhibitor, we know this is a test of the idea that we can restart the process of inducing division in supporting cells and let nature take its course from there in differentiating some of them into hair cells.

In this experiment, it looks like thresholds improve by maybe a bit more than 10 dB for the treatment group compared to about 4 dB or so for controls (first graph on page 79). Except at the highest frequencies these differences are statistically significant. It is good that they have shown some improvement, but 6-7 dB improvement over control is by no means earthshaking. It's a bit concerning that the treatment effect was smaller at high frequencies (given we typically have high frequency losses that are greater than low frequencies losses), but this looks like a function of some weird results for the controls. Unfortunately the pattern of damage was different between treatments and controls at 24 hours and the controls showed a somewhat weird pattern of recovery. All of this is likely due to small sample sizes, and it would have been nice to know the sample sizes.

I'm guessing here, but it looks like the second graph on slide 79 shows the distributions of effects for the treatment and control groups at 20 kHz - i.e., I think the heights of the blue bars add up to 100 and the heights of the grey bars add up to 100. This tells us more than the simple average effects. Assuming I am correct, we see that almost half of the treatment group sees a 10 dB improvement in threshold and over 10% see at least a 25 dB improvement. 15% or so of the controls see a 15 dB improvement (this is why there is a control group), but most see a 0 or 5 dB improvement.

More concerning is slide 80. Almost all of the restoration is coming from IHCs - even after treatment, 80% of the OHC are gone. There will need to be a significant restoration of outer hair cells to make large changes in thresholds. It would be interesting to see the distribution of increases in OHC due to treatment and see if that correlates at 20 kHz with the improvement in thresholds. I would think the animals with 30 dB improvement in thresholds at 20 kHz had the largest increases in OHC in the portion of the cochlea associated with 20 kHz.

There's a lot we don't know. First, we don't know whether these experiments were done in adult or newborn animals though I am assuming adults. Second, we don't know what other experiments have been done. I would be surprised if they showed all of their best results in a conference presentation before publication, but we don't know that. We also don't know what was said during the presentation. Will might have provided additional useful context. Third, we don't know what is going on with the OHC. Is there just more damage there? Is this treatment less effective for OHC? (Gene therapy is frequently less effective for OHC than IHC. Those papers pay lots of attention to the ability of the viral vectors to 'infect' OHCs.) If so, do they have a solution? Fourth, we don't know if there continues to be recovery after 5 weeks - either in terms of whether it gets even better or if what recovery there is goes away (though Weber suggests at least 90 day durability in animal studies). And, to answer before anyone asks, there's nothing here that tells us whether repeated applications might be more beneficial. This last point may matter in a different way than people here typically ask about because one difference between a lab culture and a clinical treatment is the amount of time the tissue is exposed to the drug. In the lab experiments described in slides 73-76, the tissue is cultured for 3 days. In that case you see large increases in both IHC and OHC. Weber does contrast Frequency's approach (a single quick procedure) with Audion's trial (3 injections) suggesting that Frequency is still planning on a single administration. Lastly, of course, aside from the rodents/humans differences, we don't know what the results might look like in animals whose hearing has been damaged in the ways ours has - over the course of a lifetime with various kinds of noise/medicine exposure rather than 2 hours of 120 dB noise with a quick administration of the treatment presumably immediately following the noise.

So not surprising though perhaps a bit disappointing. The challenge as always is the inaccessibility of the cochlea. But we won't know more until we see the next paper.

 

@Aaron123 thanks for your explanation on the matter.

I agree it might not be what we've hoped for, but (a side from the notion that we indeed do not know what is said), I remember my first Amstrad PC had 8MHz. Now I have (4x)2.8 GHz, 300 times as much. They have to start somewhere, let's hope the future is near.