Member- Dec 21, 2019
- 319
- Tinnitus Since
- 2014, 10/2019
- Cause of Tinnitus
- School Band, Noxious Car Radio
Frequency Therapeutics — Hearing Loss Regeneration
- Thread starter RB2014
- Start date
- Apr 6, 2020
- 1,031
- Tinnitus Since
- 2016
- Cause of Tinnitus
- 2016: headphones, 2020: worsened thanks to Rammstein
@Joly There's no certainty whether Frequency Therapeutics / Astellas will start screening for phase 2B in Europe straight away after they will publish the results of phase 2A in September/October, especially when Corona will still be of great concern around that time. You're from France, am I right? In that case, you can contact the French department of Astellas Pharma (responsible for trials in Europe) if they start trials in your location.
Hi, I was thinking about the cochlear implant patients, they had to go for the implant surgery on the same day! So they got no choice...then I went to check the source of the info, it seems they conducted the safety study in Australia too I think? I read that they recruited 9 subjects who were going to get cochlear implants and it was from Melbourne Australia. They met all the endpoints of their study for Australia but I'm sure they also did another one with the 23 or 15 patients in USA too. But they didn't do word scores test for Australia side I think, only in USA. I paste the info here for your quick reference. Not sure if it's old news.
"The goal of this landmark First-in-Human study was to prove the safety and tolerability of FX-322 at a dose that has been effective in restoring hearing in animals," said Stephen O'Leary, M.D., lead investigator for the study, and the William Gibson Chair of Otolaryngology at The University of Melbourne. "This goal was achieved by showing that FX-322 was well tolerated with no drug related adverse events reported. Further, the results validated the feasibility of using a standard intratympanic injection to deliver FX-322 locally to the inner ear. In addition, we found that FX-322 successfully diffused from the middle ear to the perilymph fluid in the cochlea with minimal systemic drug exposure."
The Phase 1 safety study was conducted at the Royal Victoria Eye and Ear Hospital in Melbourne, Victoria, Australia. The study enrolled 9 adult subjects with severe to profound sensorineural hearing loss who were scheduled to receive a cochlear implant in the 24 hours following intratympanic injection of FX-322. Our aim was to determine the safety and tolerability of FX-322 in the awake patient. Further, we were able to confirm the bioavailability both locally and systemically. This successful trial lays the groundwork for future trials in patients with moderate hearing loss who are not candidates for the cochlear implant and whose hearing can be studied over time.
"The goal of this landmark First-in-Human study was to prove the safety and tolerability of FX-322 at a dose that has been effective in restoring hearing in animals," said Stephen O'Leary, M.D., lead investigator for the study, and the William Gibson Chair of Otolaryngology at The University of Melbourne. "This goal was achieved by showing that FX-322 was well tolerated with no drug related adverse events reported. Further, the results validated the feasibility of using a standard intratympanic injection to deliver FX-322 locally to the inner ear. In addition, we found that FX-322 successfully diffused from the middle ear to the perilymph fluid in the cochlea with minimal systemic drug exposure."
The Phase 1 safety study was conducted at the Royal Victoria Eye and Ear Hospital in Melbourne, Victoria, Australia. The study enrolled 9 adult subjects with severe to profound sensorineural hearing loss who were scheduled to receive a cochlear implant in the 24 hours following intratympanic injection of FX-322. Our aim was to determine the safety and tolerability of FX-322 in the awake patient. Further, we were able to confirm the bioavailability both locally and systemically. This successful trial lays the groundwork for future trials in patients with moderate hearing loss who are not candidates for the cochlear implant and whose hearing can be studied over time.
Stupid question... I'm sure I'm misunderstanding this. The test subjects had decided to get implants, so if the FX-322 damaged their ears... not an issue. But were these the same cochlears that were looked at under a microscope?
I was looking at Frequency Therapeutics expanded use access and this is what was stated:
"Frequency Therapeutics understands that some patients may wish to access investigational medicines that are not yet approved by the FDA and other regulatory authorities".
When they mean by other regulatory authority does this mean that someone outside the USA could potentially get expanded use access in their country. Would that mean it would have to go through Astellas Pharma since they hold the international rights or could we still potentially get Frequency Therapeutics to give us access outside USA?
"Frequency Therapeutics understands that some patients may wish to access investigational medicines that are not yet approved by the FDA and other regulatory authorities".
When they mean by other regulatory authority does this mean that someone outside the USA could potentially get expanded use access in their country. Would that mean it would have to go through Astellas Pharma since they hold the international rights or could we still potentially get Frequency Therapeutics to give us access outside USA?
Yes the test subjects for Phase 1 wanted to get a cochlear implant so they got FX-322 injected in the ear to see if it was safe and they used the patient's removed cochlear to look at it under a microscope.
Sorry @Lucifer but I think you cannot get a cochlear implant to work without a cochlear (even though it is a damaged one). The human cochlear we saw on the Frequency's website was a donated one, from a person who was undergoing surgery for a brain tumour and the rest of which we saw were from mice I think.
@Fanny1, if you were thinking how did they manage to know if the drug got into the cochlear, I searched some info on the first study, I am pasting some of it here for your reference. It mentions aomething about 'pharmacokinetics', not sure how they measured that? Perhaps during the cochlear implant surgery they could somehow get a sample of the fluid in it?
@Fanny1, if you were thinking how did they manage to know if the drug got into the cochlear, I searched some info on the first study, I am pasting some of it here for your reference. It mentions aomething about 'pharmacokinetics', not sure how they measured that? Perhaps during the cochlear implant surgery they could somehow get a sample of the fluid in it?
Hi, sorry, I just found out that they actually measured samples of steroids from guinea pigs' cochlear... these guinea pigs were delivered steroids through a cannula in their cochlear implant and they took samples to measure the steroid amount at different timings... but I guess for the FX-322 study they could only take one sample, and that would be the instance where the cochlear implant was inserted... do you think so? So they proved by measuring locally in the cochlear that the drug diffused passed the round window and was present in the cochlear. But can you actually draw out fluid from the cochlear without negatively affecting a person's balance and hearing?
I've seen other studies do the same thing - first test for safety on people with severe hearing loss, so if the drug isn't safe, you don't hurt them as much as people with only moderate hearing loss.
At the same time, safety issues might pop up during subsequent trials in which subjects with better hearing would be more sensitive to harm.
At the same time, safety issues might pop up during subsequent trials in which subjects with better hearing would be more sensitive to harm.
- Mar 14, 2020
- 180
- Tinnitus Since
- 12/19
- Cause of Tinnitus
- Noise Exposure + Viral Infection
Does anyone know if it's possible to over-regenerate? Like could the treatment regrow too many hair cells, or could it be problematic to get 'FX-322 2.0' once they come out with the new formulation if you already received the original?
I played around with more online hearing tests more today and also set my computer's headphones in Windows to a 80 left ear/100 right ear balance (before it was 100/100). This more or less makes audio such as podcasts seem more even to me. If I have hearing loss across all frequencies in my right ear, I'm wondering how much FX-322 will really help. Then again maybe I have slight hyperacusis in my left ear? I should probably go get a standard audiogram...
Maybe I'm overthinking this; pretty sure @FGG has posted in this thread before about how important the higher frequencies are and how they can make things in the lower frequencies seem quieter, too. Probably giving my ears too much of my brainpower this week... it's hard to not think about it, though.
I played around with more online hearing tests more today and also set my computer's headphones in Windows to a 80 left ear/100 right ear balance (before it was 100/100). This more or less makes audio such as podcasts seem more even to me. If I have hearing loss across all frequencies in my right ear, I'm wondering how much FX-322 will really help. Then again maybe I have slight hyperacusis in my left ear? I should probably go get a standard audiogram...
Maybe I'm overthinking this; pretty sure @FGG has posted in this thread before about how important the higher frequencies are and how they can make things in the lower frequencies seem quieter, too. Probably giving my ears too much of my brainpower this week... it's hard to not think about it, though.
Interesting. Inserting the electrode array into cochlea seems like a risky procedure, though. Even so—it's pretty amazing that people who were born deaf, for example, might still experience sound this way.Hi @Lucifer , here's something I found about cochlear implants if you're interested!It may not be the same as normal hearing, but it's like a miracle for people who hear its sounds for the first time.
Good question. I suppose the regeneration would happen over a longer period of time, like weeks or months, giving your brain time to adapt.
From then onwards, you can use high pitch shrieks and your bat-like hearing to navigate in the dark without a headlamp too.
Indeed. They place the electrode array in the cochlea, thereby destroying any remaining natural hearing.
Hi, I agree that safety issues are not as reflective in such a small group compared to a large group, but honestly I'm keen to find out more
and no offence meant, which were the studies that used drugs on people with severe hearing loss.
- Dec 21, 2019
- 319
- Tinnitus Since
- 2014, 10/2019
- Cause of Tinnitus
- School Band, Noxious Car Radio
I believe they released a statement that their drug cannot over regenerate based on preclinical data.
The CI electrodes do not contact with the whole cochlea. The idea is to preserve natural hearing in the areas where the recipient has any functional hearing.
The Hough Pill's current trial is in fact aimed at reducing the damage of surgical trauma and minimizing the hearing damage to adjacent parts of the cochlea.
- Feb 19, 2020
- 65
- Tinnitus Since
- 11/2017
- Cause of Tinnitus
- Jet Engines, Concert
In intact cochleae they got a doubling of IHC and OHCs which indicated a limiting or clamp down factor on the regeneration process.
See Will McLean's YouTube around 18:00:
HootOwl
Member
I don't think progenitor cell activation has this issue, based on what several other members have mentioned. With notch inhibition things could potentially get a bit dicier.
We know that Pipeline only activates Notch in a limited way and has confirmed their compound regenerates morphologically correct OHC, but Audion induces Notch much more extensively (and potentially haphazardly) - hence the reluctance for some of us to try Audion despite it most likely being the first to market.
Agree, Frequency didn't find any morphologic changes to suggest this would be a problem and in an email I received, Pipeline doesn't see this as a problem for their drug either. Audion? Who knows. It has potential to be a problem.
But just for clarification, Gamma secretase inhibitors inhibit the Notch pathway, not activate it.
HootOwl
Member
- Mar 16, 2017
- 102
- Tinnitus Since
- 10/15 got worse 11/16
- Cause of Tinnitus
- Earbuds, inner ear infection NHL and high frequency loss
Sorry, late to the party. They can get hair cells to regrow but can they get the neurons to reconnect to the brain? I don't want to be greedy if they can give just 10-15 dB back that would be awesome.
The regenerated hair cells will reconnect and synapse with the spiral ganglion neurons. If you have synapse damage without hair cell damage in a particular location, this drug will not address this but there are other drugs in trial for that.
- Mar 14, 2020
- 180
- Tinnitus Since
- 12/19
- Cause of Tinnitus
- Noise Exposure + Viral Infection
The regenerated hair cells also come with synapses which connect to main auditory nerve. The two main suspected limitations of this drug are:
1.) It doesn't regenerate synapses where hair cells are still intact. The Hough Pill apparently specializes in this area though and should be out in a few years.
2.) It only seems to reach around 6.5 kHz, not lower than that. Hopefully increased dosing during the current phase 2a trial will show some improvement here.
If not, we'll have to wait for a new delivery vehicle for FX-322 to regenerate those lower frequencies, which may take another year or 2 after the current formula is released.
Do you have a 6.5 kHz sound sample? I found 6.5 kHz (6500 hz) on YouTube but it is really trebly. My current tinnitus is trebly but no too high frequency. No improvements in volume...
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