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.
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