Rogue Immune Cells Tied to MS Point to New Drug Target

Researchers identified a possible culprit for immune cells’ resistance to regulation in a small study of multiple sclerosis patients, suggesting a potential new target for treatment.

T-cells, when working properly, are an important part of the immune system’s arsenal for fighting off invaders. In MS patients, however, they can ignore the controlling orders from regulatory cells and attack the central nervous system. In a study published today in the journal Science Translational Medicine, researchers found one reason this happens in MS.

Scientists at the Benaroya Research Institute and Virginia Mason Medical Center in Seattle identified a protein called interleukin-6, or IL-6, as a reason for those cells going rogue in patients with relapsing-remitting MS, the most common form of the disease.

“We identified a new problem in multiple sclerosis that hadn’t been identified before,” Jane Hoyt Buckner, an author of the paper and associate director of Virginia Mason’s Benaroya Research Institute, said today in a telephone interview. “Then we were able to show why that happens in MS patients, which is this enhanced responsiveness to the cytokine IL-6.”

People with relapsing-remitting MS have more receptors for IL-6 on the surface of their T-cells, suggesting IL-6 may be a good target for therapy, Buckner said.

More than 2.1 million people worldwide have MS, a disorder of the central nervous system that can cause numbness of the limbs, trouble walking and vision loss, according to the National Multiple Sclerosis Society. The most common form is relapsing-remitting, characterized by sporadic attacks that degrade neurological function, followed by periods of recovery.

Cell Differences

In the study published today, researchers looked at blood samples from 24 patients with relapsing-remitting MS who weren’t taking immunomodulatory therapies. In addition to observing the implication of IL-6, the scientists also noted cellular differences among patients based on the severity of their disease in the previous two years.

“In people with well-controlled or mild MS, we didn’t see this escape of T-cells” from regulatory control, Buckner said. “But we did see it in patients who had more active disease over the previous two years.”

That suggests that T-cells’ resistance to regulation could be a helpful biomarker for determining the course an MS patient’s disease might take in the future, Buckner said. She cautioned that studies would need to be done to test the hypothesis as a predictive tool.

Treatment Strategies

Such information about disease course may help doctors decide which medicine to prescribe. If a patient’s disease looked to be more active, a physician might opt for a more aggressive therapy, such as Biogen Idec Inc.’s Tysabri, over a milder therapy such as the Biogen’s Avonex or Teva Pharmaceutical Industries Ltd.’s Copaxone.

The findings also hint at the potential for new MS drug development, the researchers said. At least one medicine that targets IL-6 is on the market, tocilizumab, sold as Actemra by Basel, Switzerland-based Roche Holding AG, and others are in clinical testing. Actemra is used in rheumatoid arthritis.

“You would think that, potentially, if you could block this receptor or actions of IL-6 on these cells, you might return their normal sensitivity to regulation and that way you could suppress the immune response to the central nervous system,” Bruce Bebo, associate vice president of discovery research at the National Multiple Sclerosis Society, said in a telephone interview. He wasn’t involved in today’s research.

Further Study

Bebo warned that the immune system is complicated and IL-6 may be involved in other areas that would make its use as a drug target more difficult.

The researchers confirmed the results in two separate studies with small numbers of people -- the first in 14 patients with relapsing-remitting MS, and the second in 10, Buckner said. They compared the samples to those from people without MS.

“Now that we have this finding, it’s exciting and it holds the promise of us being able to determine who has more severe disease and identify a group of patients that would respond to therapy targeting the IL-6 pathway,” Buckner said. “Now we have to do the studies to thoroughly show that’s true before we can apply it to patients.”

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