When The Body Attacks Itself

Young: The imperative in the pharmaceutical industry, when—you're thinking about investing nearly a billion dollars in a program, is to have deep knowledge of the molecular pathways you're going to be focused on. There's this sea of noise that's hard to get through when you're looking for drug targets, unless you have a very small group of genes to look at. Here, we have that-we have the opportunity to take many, many, many autoimmune diseases and search more quickly because we've narrowed down the genes that are involved.—Considering what drives the industry, this gives them a real leg up on developing cures.

What if you narrowed it down further? Could a drug for all of these disorders be aimed at Foxp3, the master controller of these 30 genes?

Young: It's an option. If you find some secret sauce that will modify Foxp3's activities and you've shown that this is critical to a broad spectrum of disorders, that's going to be a great thing. Let's say for the sake of speculation that in one of these diseases, Foxp3 itself is not working at adequate levels or is slightly defective. That would make it a single target we could go after and see if we could tune it up. On the other hand, it could turn out-as it usually does-that life's more complex than that. For each one of the diseases, there may be some subset of the 30 target genes that aren't working right, and we'd have—to use another, mo—e specific approach in each disorder.

Marson: One of the key next steps is to take each of these 30 genes and figure out what they're doing within the T cells. There's evidence that they play important roles, but the molecular underpinning of that is really still unknown. The other thing will be to look for chemicals that mimic the function of Foxp3. There may be some that are already known, but hopefully there will be more to be discovered in the future.

Could you also manipulate these genes in healthy people to suppress the immune system if you needed to, the way doctors do now in organ transplantations?

Young: Sure. In the same vein that you can imagine the loss of function of these genes, you can think of situations where you'd like to turn down the immune response, like in transplantation. There are already drugs that do that, of course, but the best evidence we have so far is that those drugs are working in a different way, on different genes than the ones we've discovered. Then again, sometimes if you discover new genes and then you go and test what the known drugs are doing, you're often surprised that they're doing multiple things and are involved in pathways you didn't anticipate.