5 ms·

“Animal research has shown that natural cochlear hair cell regeneration and resultant hearing restoration is very real” - Although exciting, we also need to rem

“Animal research has shown that natural cochlear hair cell regeneration and resultant hearing restoration is very real” - Although exciting, we also need to remember that translatability rates from animal models to humans is notoriously low, usually in the single digits for most therapeutic areas. This is some cool tech, but just wanted to point it out that success in animal models =/= we will eventually get to see the realized treatment.

gumby 4y ago
> Although exciting, we also need to remember that translatability rates from animal models to humans is notoriously low, usually in the single digits for most therapeutic areas. This is true of humans as well -- there are plenty of programs that get interesting and clear results in Phase 2 (the dose ranging phase: essentially "what dosage is most efficacious") that die in Phase 3 (roughly: "OK, how does that dose really work on a statistically significant population that also represents the demographics of the country"). These studies are so expensive that nobody goes into Phase 3 unless they believe Phase 2 pretty certainly demonstrated that the drug works, and well. It's also hard to figure out just how the animal's hearing is improving (you can't simply ask). I'm sure they have some experiments, but growing the hairs back may be necessary but not sufficient. Look at all those Alzheimers programs aimed at removing the plaque that haven't demonstrated any value in the clinic. The plaque might not even be alzheimers itself -- it could merely be the body's response to some different underlying effect of the disease. The choice of animal is very important, and the FDA cares a lot. Mice are popular because they are cheap. I worked on a program years ago that used guinea pigs because mice couldn't get the disease. We didn't use rats as the compound caused cancer in rats, and someone else had had their program derailed because the FDA required a separate analysis and study to demonstrate that the cancer was specific to rats and not other species (rats get lots of cancers). For our program the FDA required some studies in (non-guinea) pigs before they were willing to allow any human trials.
- JohnBooty 4y ago
  It's also hard to figure out just how the animal's hearing is improving (you can't simply ask) This seems relatively easy, right? Play a sound at a given frequency, associate it with a food reward. Like Pavlov's dog, but vary the frequency of the bell. Oversimplification obviously, and "easy" is extreme relative to all the other hard parts involved but that part seems very doable
  - Traubenfuchs 4y ago
    I guess you can easily damage a rats/monkeys hearing consistently (may we find peace for our sins) and I guess you can easily strap those animals into an MRI or strap an EEG measuring device onto one. Seems simpler than training a significant amount of them!
  - jacquesm 4y ago
    Experimental design in medical trials on animals is extremely complex.
  - ddingus 4y ago
    Well, there's more to it than binary to text you. I agree with you, in that the signaling perception is probably easy. However, let's say that that frequency is coupled with several others, making for noise for poor discrimination. For that kind of thing, we're going to need real people who can communicate in detail.
    - gumby 4y ago
      Yeah, fitting and tuning a hearing aid is quite complicated, and there are intelligent people at both sides of the process.
  - gumby 4y ago
    One sobering lesson from my time working in the life sciences is that everything is insanely complex and once you've isolated everything in your problem space into a small, relatively isolated set, you still end up with an insanely complex space. Essentially it's fractally complex.
- crackedbassoon 4y ago
  Unlike your Alzheimer’s example, hair cell loss is definitely the cause of hearing loss in many cases. There are other possible causes but this is the first or second most common biological antecedent. Basically, if we can regrow them, there’s a good chance of restoring hearing, provided the rest of the auditory system hasn’t atrophied too badly.

gumby 4y ago

> Although exciting, we also need to remember that translatability rates from animal models to humans is notoriously low, usually in the single digits for most therapeutic areas. This is true of humans as well -- there are plenty of programs that get interesting and clear results in Phase 2 (the dose ranging phase: essentially "what dosage is most efficacious") that die in Phase 3 (roughly: "OK, how does that dose really work on a statistically significant population that also represents the demographics of the country"). These studies are so expensive that nobody goes into Phase 3 unless they believe Phase 2 pretty certainly demonstrated that the drug works, and well. It's also hard to figure out just how the animal's hearing is improving (you can't simply ask). I'm sure they have some experiments, but growing the hairs back may be necessary but not sufficient. Look at all those Alzheimers programs aimed at removing the plaque that haven't demonstrated any value in the clinic. The plaque might not even be alzheimers itself -- it could merely be the body's response to some different underlying effect of the disease. The choice of animal is very important, and the FDA cares a lot. Mice are popular because they are cheap. I worked on a program years ago that used guinea pigs because mice couldn't get the disease. We didn't use rats as the compound caused cancer in rats, and someone else had had their program derailed because the FDA required a separate analysis and study to demonstrate that the cancer was specific to rats and not other species (rats get lots of cancers). For our program the FDA required some studies in (non-guinea) pigs before they were willing to allow any human trials.

JohnBooty 4y ago
It's also hard to figure out just how the animal's hearing is improving (you can't simply ask) This seems relatively easy, right? Play a sound at a given frequency, associate it with a food reward. Like Pavlov's dog, but vary the frequency of the bell. Oversimplification obviously, and "easy" is extreme relative to all the other hard parts involved but that part seems very doable
- Traubenfuchs 4y ago
  I guess you can easily damage a rats/monkeys hearing consistently (may we find peace for our sins) and I guess you can easily strap those animals into an MRI or strap an EEG measuring device onto one. Seems simpler than training a significant amount of them!
- jacquesm 4y ago
  Experimental design in medical trials on animals is extremely complex.
- ddingus 4y ago
  Well, there's more to it than binary to text you. I agree with you, in that the signaling perception is probably easy. However, let's say that that frequency is coupled with several others, making for noise for poor discrimination. For that kind of thing, we're going to need real people who can communicate in detail.
  - gumby 4y ago
    Yeah, fitting and tuning a hearing aid is quite complicated, and there are intelligent people at both sides of the process.
- gumby 4y ago
  One sobering lesson from my time working in the life sciences is that everything is insanely complex and once you've isolated everything in your problem space into a small, relatively isolated set, you still end up with an insanely complex space. Essentially it's fractally complex.
crackedbassoon 4y ago
Unlike your Alzheimer’s example, hair cell loss is definitely the cause of hearing loss in many cases. There are other possible causes but this is the first or second most common biological antecedent. Basically, if we can regrow them, there’s a good chance of restoring hearing, provided the rest of the auditory system hasn’t atrophied too badly.