GOAL: TREATMENTS FOR 7,000 KNOWN RARE DISEASES

that rare going forward.

Because some rare diseases are relatively easy to find a treatment for, and others aren’t?

In every case we’ve tried so far, we’ve found something. We’re just finding existing drugs that already work.

These are drugs that have already been approved for other purposes?

Repurposing is a key step in addressing rare diseases and avoiding the huge costs that come with novel drug development. What you really want to do is test all the approved drugs that are out there.

Are some diseases particularly suited to this approach?

Ion channel-driven epilepsies — epilepsies where there’s a clear electrophysiological origin. These kind of occupy a sweet spot where it comes to finding treatments. They’re kind of accessible with drugs. Many approved molecules will hit them incidentally, even though that’s not what they’re trying to do.

Obviously, not every rare disease is as easy to find a treatment for.

You do have large classes of diseases where it’s not that simple. You can’t directly target the root cause.

Is this personalized medicine the future for all of us?

Personalized or precision medicine is absolutely the future — not just because it’s better care, but long-term, it will also reduce cost. Ultimately, by delivering the right drug to the right patient at the right time, it’ll get cheaper, too.

Are we there yet?

I think we are at an inflection point. The costs have come down to the point where it’s reasonable to start to do this for basically everybody. A pharmacogenetic panel that will tell you your response essentially to every drug on the market costs on the order of $300. And you’ll have that data for the lifetime of the patient. We’ll sequence everybody at birth at some point.

But is knowing a genetic blip that causes a disease enough to learn how to treat it?

Right now there’s a gap between diagnostics and therapeutics. Genetics has gotten really good at telling patients what they have, but not what to do next.

That’s the focus of your current work — to come up with a road map for other families to follow in their search for a treatment?

That’s really the goal of my life right now: to systematize the entire process of finding treatments, so it’s less art and more focused science.

One of the things I’m building as part of my institute at UAB is the infrastructure necessary to take a patient from diagnosis to a therapy.

This is uncharted territory for physicians. They’re not used to saying, “What you need to do next is a science experiment.” But for many of these rare diseases, that’s exactly what you have to do.

What kinds of experiments?

It might be building a worm or a fly and testing it. It might be a chemical screen, where you start testing compounds against a cellular or animal model. Or it could be a genetic screen where you’re looking for other genes that interact with the gene driving your disease.

We craft a research plan for them and say, “This is the way you need to go,” and even connect them with the right researchers to make that next step.

Is it really feasible for one family or a small number of people to develop their own personalized treatments?

As you network these companies and institutions together, it’s changing drug development from this insurmountable process into something that’s actually quite achievable for individual patients or patient foundations.

Do companies see enough of a financial interest in developing a drug to treat just a few hundred patients?

I’ve seen companies get involved in shockingly small diseases. Patient foundations have a major role to play in “de-risking” the science around therapeutic development. If they “de-risk” it enough, companies will jump in.

Your ultimate goal is to find a treatment for all 7,000 known rare diseases.

For all 7,000 now, and however many more remain to be found.

Is that realistic?

Whether it’s realistic or not, it’s a moral imperative that we do it. So, we’ll do it one at a time. I’ve learned it’s not so helpful to focus on what’s possible or realistic anymore. Just focus on the next step, keep taking next steps, and see how far you can go.

And how is Bertrand doing now?

He’s very happy. He’s definitely got some severe developmental problems that will be difficult to correct. If we’d intervened earlier, he might be better off now. I’m more optimistic about the next generation of patients.

I look at things like stem cells and regenerative medicine to see if there might be some way to get Bertrand what he’s never had an opportunity to have in the first place. There are several next steps. I’m just getting started.