Dr. Sergiu Pașcă

There's a lot of stochastic forces in development.

And if a cell, it's much faster at opening the other gene, like the similar gene that is unmutated, and in the other case it wasn't, or maybe there are other environmental factors that are interacting.

But the other possibility is that the genetic background that we have is very different.

And so we're still like in early days of truly understanding what are the effects of the genetic backgrounds in modulating the severity of these conditions.

But in itself, it's a very interesting question.

Why some individuals can have a massive deletion of 60 genes and yet still move around?

So I think that's going to be a lot of interesting biology to discover behind this.

And then, of course, we know that there are differences between animals and humans.

That we already know, that very often a mutation that would be very severe in a human has almost no defect in an animal model, partly because that gene maybe plays a different role or perhaps the genetic background is very different.

So, Timothy syndrome has sort of like been the first example, partly because it was some of the first neurons that were derived from iPS cells and from patients with neurodevelopmental disorders in those early days, and also partly because it's the disease that we studied so much on all possible angles, first with 2D neurons, then with 3D organoids, then with assembloids, that at one point...

And I like to say that a therapy became self-evident, so to speak.

I mean, we were honestly not, I was not thinking that we would develop a therapy for Timothy syndrome, like not in the near future.

But at one point, we just accumulated enough biological information that you just look at it and you say, oh, this is exactly what we need to do.

And it turns out that, and this we did about like five years ago, that we understood so well how this channel is processed in the cells and what it causes, that at one point we realized that all we need to do is generate this tiny piece of nucleic acid

that we can get inside the cells, it will go in, switch the way the channel is actually processed and rescue or reverse the phenotypes.

And it turns out that every single defect that we've described over the past 15 years in the studies can be rescued by just adding the tiny piece of nucleic acid.

It's almost like a gene therapy in a way.

It just doesn't involve a virus.

And so this is the first disease and we're preparing for a clinical trial.

These patients are very rare.