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2 Types of MS, Study Reveals

Blood Test Would Predict Success of Multiple Sclerosis Treatment

By Daniel J. DeNoon
WebMD Health News

Reviewed By Laura J. Martin, MD

March 29, 2010 - New study findings may soon revolutionize multiple sclerosis (MS) treatment and diagnosis.

The study strongly suggests that there are two major types of MS and that a simple blood test can tell one from the other. By itself, that would be a major finding. But that's not all.

One type of MS responds to beta interferon, generally considered the best treatment. The other type does not -- and beta interferon treatment may even make it worse, find Stanford University researcher Lawrence Steinman, MD, and colleagues.

"I'm very excited about some of the implications of this," Steinman tells WebMD. "The most important implication is that a simple blood test could tell us who does and does not respond to beta interferon. It could be that about 25% of patients are in the 'do not benefit' group."

For patients who do respond to beta interferon, the study raises hopes that the drug may work better than previously thought. That's because the clinical trials that proved beta interferon to be effective likely enrolled both types of MS patients, watering down the drug's average efficacy in beta interferon responders.

In coming months, Steinman said, he hopes to show that the two kinds of MS respond differently to other MS drugs, too.

Patricia O'Looney, PhD, vice president for biomedical research at the National MS Society, said the study will help researchers solve some of the mysteries surrounding MS.

"No two people with MS are exactly alike in disease course and in response to therapy. Why is this?" O'Looney tells WebMD. "We don't understand why about 50% of people who take beta interferon don't respond well."

Two Routes to MS

Multiple sclerosis is an autoimmune disease caused by haywire immune responses that attack the myelin sheath protecting nerve fibers in the central nervous system. The culprits are lymphocytes called CD4 T helper cells, sometimes called the quarterbacks of the immune system.

In MS, a subset of CD4 cells called Th1 cells direct an inflammatory immune response against myelin. Beta interferon dampens this signal, so it's a great help to people with MS -- at least, to those who respond to treatment.

Why doesn't beta interferon always work for MS patients? A clue comes from a little known but equally devastating disease called neuromyelitis optica (NMO). In NMO, the immune system attacks nerve fibers, but it targets a protein different fromyelin, says NMO researcher Michael R. Yeaman, PhD, vice chair of medical sciences at Harbor-UCLA Medical Center.

NMO researchers have shown that the CD4 cells behind NMO aren't Th1 cells, but another type called Th17. Might Th17 cells cause some cases of MS?

Yes, Steinman and colleagues found. First the researchers induced an MS like disease in mice using either autoimmune Th17 or autoimmune Th1 cells. Then they showed that beta interferon improved MS-like symptoms in mice with Th1-induced disease, but that the drug worsened MS symptoms in mice with Th17-induced disease.

Humans, too, appear to have different kinds of MS. Steinman and colleagues tested blood samples taken before treatment from 26 MS patients. Six of the 12 patients who did not respond to beta interferon had high levels of Th17 in their blood.

These patients with Th17 immune responses also had high levels of beta interferon in their blood -- before beta interferon treatment. That means one of two things:

  • In patients with Th17-type MS, beta interferon doesn't help because beta interferon levels already are high.
  • In patients with Th17-type MS, beta interferon doesn't fight inflammation -- it makes inflammation worse. In this case, just as in mice with Th17-induced disease, beta interferon would exacerbate MS.

New Hope for MS Patients

"We are very excited about this kind of discovery, because there are new therapy approaches that focus on Th17 immune pathways," Yeaman tells WebMD. "We don't know the answers yet, but we are starting to see the dots on the page -- and if we can connect the dots, perhaps a new treatment or cure can emerge."

People with MS are likely to see a benefit long before new treatments emerge. Blood tests already exist that can tell MS patients whether they have Th1 or Th17 disease. Those with Th17 disease can be spared having to undergo the side effects of beta interferon treatment, while those with Th1 disease can endure side effects knowing that the treatment is highly likely to work.

"When first diagnosed with MS, the first question a person asks is, 'What can I expect? How bad will it be?'" O'Looney says. "It would it be great if we can identify something to say, 'This person has this makeup and 10 years from now may be OK, or that person may need more aggressive therapy."

Despite their enthusiasm over the new findings, all of the experts consulted for this article caution that the new findings must be validated in large numbers of MS patients. All warn that it's too soon for patients to seek testing or to make treatment decisions on the basis of these preliminary findings.

The study findings appear in the March 28 advance online issue of Nature Medicine.

SOURCES:

Axtell, R.C. Nature Medicine, advance online publication, March 28, 2010.

Wekerle, H. and Hohlfeld, R. Nature Medicine, advance online publication, March 28, 2010.

Larry Steinman, MD, professor of neurology and neurological sciences, pediatrics, and genetics; and chair, interdepartmental program in Immunology, Stanford University, Stanford, Calif.

Michael R. Yeaman, PhD, professor of medicine, Geffen School of Medicine, University of California, Los Angeles; and vice chair for medical sciences, Harbor-UCLA Medical Center, Los Angeles.

Patricia O'Looney, PhD, vice president biomedical research, National MS Society.

© 2010 WebMD, LLC. All rights reserved.



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