@Diesel
I read the paper you posted about IHC loss and central gain. The following diagram provides me with a theory about what could happen with my problem over the course of years -- loudness hyperacusis getting worse and worse until it just breaks and I'm mostly deaf. It's not just IHC, but also the auditory nerve fibers.
Several things from your paper that I found interesting:
- Removing the third row of OHC from styrene administration does very little to decrease amplification
- The average 54 year old man has ~10% OHC loss and ~0% IHC loss, while the average 89 year old man has 10-40% OHC loss and ~10% IHC loss. There's also a huge gap in synapses lost, leading to the theory that synapse loss is a precursor to IHC loss.
I'm a little confused about your (and
@FGG's) theory regarding FX-322. So the hypothesis is that it
may work for IHC and do nothing or very little for OHC. If I am understanding the picture correctly, wouldn't it seem like if IHC are regrown, then the first layer of OHC will be regrown? But I thought the first two layers were the most important and the third layer wasn't.
More doubts about the severe group: Okay, sure,
if IHC really are regrown first, then this is the group that should see the most cochlear gains. But will it show up even if it was there? I ask because there seems to be a sudden difference between little IHC loss accompanied by central gain versus so much IHC loss and disastrous WR scores. Is it possible that the drug helps IHC loss a
little bit, but not enough to really do anything?
That's not a defense of the drug, as it would still be a failure. I just don't really understand how the results are going to look so beautiful.
I'm also concerned about the one person from Phase 1/2 who had plenty low enough WR to improve, but didn't at all. Their improvement easily fell within the margin of error. What is going on with this person? It's just one person, but we are also using only three people to paint the drug in a positive light.
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