Otoferlin

That’s DFNB nine, yes.

The OTOF gene produces a protein called otoferlin, and otoferlin is what the hair cells, the keys, need to fire signals across the auditory ribbon synapse to the auditory nerve.

In this specific condition, that protein is simply absent.

The cochlear anatomy is intact.

That's not philosophy.

That's a concrete asymmetry.

And bioethics sources have actually flagged framing OTOF deafness as something requiring genetic correction as contested in itself, not just around implants, but this specifically.

The Alexander Graham Bell Association's coverage lands on the side of treatment, and that's an institutional voice, but it's not the only one in the room.

So we had actually worked on a number of other forms of genetic deafness, looking at other genes and we didn't have nearly the success that we had with that first three mouse model that we were looking at.

And we've had no, nothing worked as well as the Otoferlin gene that we stumbled upon.

So, and part of that is because a lot of these forms of genetic deafness lead to degeneration of the cells very early on.

sometimes even during development in utero.

Here is Ryan's question.

First of all, the data that Regeneron has published on their Otoferlin trial is incredible.

It's inspiring to see the amount of progress that's been made there.

But I'm curious when we will see some outcomes that show how these kids with otoferlin understand speech, because we've seen a lot of data that shows that their hearing sensitivity is improving with the gene therapy and that their neural responses measured by the auditory brainstem response are improving.

And I think it definitely sets a framework for how we move forward with future gene therapy programs.

But it's important to remember that every target is going to have its own challenges.

And, you know, I think being able to adapt and be flexible and really approach any future target with as much information and knowledge, both preclinical and clinical, that we have can ensure that in utilizing the framework set by these Otoferlin clinical trials that we can really push other targets more successfully into the clinic.

Right.

So for instance, the FDA-approved drug called Otarmony, which is from Regeneron, it was FDA-approved in April, and we started dosing children at Boston Children's in August.

That actually has a functional copy of the Otoferlin gene and uses an adeno-associated virus, a virus that's been shown to be very safe over decades of work, and that provides a functional copy of the gene.

One of the things that is tricky about treating these diseases is that they're so unique to each patient, and yet there are so many people affected by them.

400 million people worldwide, half of whom are children, have one of these rare diseases.