Three Big Questions for MS: Daniel Pelletier

Daniel Pelletier, MD

Daniel Pelletier, MD (Photo by Christopher Bazin)

MULTIPLE SCLEROSIS research has made great strides in the last few decades, but questions remain. Daniel Pelletier, Keck Medicine of USC’s vice chairman of research in the department of neurology, explains.

Why do people develop MS?

We don’t know the cause of MS. We have a working hypothesis. Patients have a genetic susceptibility; that’s where it starts. That doesn’t mean you have one gene that causes the disease, but you have a genetic background that will make your immune system prone to attack your own body. There are almost 200 genes that have been identified already that affect MS risk. But genes are not enough. On top of that there are environmental factors that raise risk, such as low vitamin D, smoking and high body mass index. It’s not just bad MS genes or bad environmental factors: It’s the interaction between the two.

The million-dollar question is, is there a virus or a bacterium that’s associated with the risk of MS? We believe that there might be a viral agent, but we haven’t been able to pinpoint which one it is. The theory is that when you are a teenager you get infected by a virus. You barely have symptoms; you are able to fight the infection. Years later, the immune cells fighting against that virus find their way into the brain and spinal cord, and now they think they see the same virus again. But it’s not the virus, it’s a portion of your myelin. Instead of the virus, the immune system is attacking the central nervous system. Years later, new symptoms may appear again, affecting different parts of your myelin and nervous system.

Is there any hope for restoring the damaged nervous systems of people already harmed by MS?

Over the past 20 years we’ve made a lot of progress on treating the inflammation. We can prevent new scars from forming, which is good. The challenges moving forward will be to prevent nerves from getting hurt.

Right now there are many researchers and companies working on myelin repair, and there are many potential candidates. Within the last few months we’ve heard the final results from a proof-of-concept trial on a promising drug for myelin repair, an antibody targeting LINGO-1.

[LINGO-1 is a protein found in nerve cells and cells that make myelin.]

What stands in the way of developing medicines that protect nerve cells?

One challenge that we have is, how do we actually monitor myelin repair? We do not have the right tools. Industry partners and researchers are in trouble right now because of that; it’s a key area of research. Without the tools, we’re not moving as fast as we should.

That’s where imaging comes in. We’re working very hard to find imaging markers for myelin repair and nerve death. The tools that we have—standard MRI and PET—are not good enough. This is an unmet need; it’s crucial. We at USC are up to this challenge.

By Amber Dance

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