Saturday, October 22, 2011

Biomarkers to guide MS therapy: Moving from "sledgehammer" to "scalpel"

Writer, ms.about.com

Every 2 years the Multiple Sclerosis International Federation awards The Charcot Award for Lifetime Achievement in MS Research. This year the award was given to Larry Steinman, Professor of Neurology at Stanford University. He was chosen, in part, for a series of studies looking at molecules involved in disease that led to Tysabri. I was lucky enough to be at ECTRIMS 2011 and see Dr. Steinman accept his award. I have to admit to becoming a little emotional when Dr. Steinman took the podium and said, "Though I'm deeply honored, let's have the real celebration when the disease is something we can see only in the rear view mirror." He is currently working on a DNA vaccine for MS, as well as finding biomarkers to guide therapy, which he discussed in his talk. I will attempt to paraphrase and summarize Dr. Steinman's presentation on biomarkers.

A "biomarker" is something in our body – for instance, a certain cell, hormone or something on our DNA – that could give clues about a disease or if a treatment is working. We could use the drugs that we have better and develop more specific drugs for MS if we could find out exactly what a person's immune system is responding to. We could then isolate the cells that are targeting the myelin and shut them off.

There are starting to be success stories in using biomarkers to guide treatment.

A couple of years ago, it was discovered that people with neuromyelitis optica (NMO), another autoimmune disease that is similar to MS, had high levels of IL-17 (Interleukin-17, a protein made in the immune system) in their spinal fluid. There are several papers in the literature that show that if you give people with NMO interferons (namely Betaseron and Avonex), they get worse.

This led researchers to wonder if people with MS who had high levels of IL-17 would not be good candidates for interferon-based medicine. Sure enough, preliminary data indicated that about half of the people with MS who have high levels of IL-17 may be "non-responders" to interferon-based disease-modifying therapy (DMT).

While it would be great to have a test that would tell you a definite "yes" or "no" to determine if an interferon DMT would work, larger studies failed to get a solid correlation. At this point, testing for IL-17 only works for 10% of people (those "outliers" with very high levels of IL-17), indicating that interferon treatment in these people has very little chance of working. However, this information would be valuable to know for those 10%. Dr. Steinman thinks that we are still at least five years away from having a licensed test to determine drug choice.

One big success in using biomarkers to guide therapy, however, is the anti-JCV antibody test to determine risk of PML in people who are considering starting (or continue taking) Tysabri. If this test is positive, the risk of PML in someone on Tysabri is one in several hundred. However, if the test is negative, the risk is miniscule.

However, biomarkers are not just to tell us what existing medications will work best. If we can find out exactly what a person's immune system is responding to, we could isolate the cells that are targeting the myelin. We could then create drugs to target just those cells.

At this point, we still do not know exactly what the immune response is in MS. Therefore, we have a "sledgehammer" approach, as many of our drugs involve modulating or deleting a large part of the immune system. By taking this approach, we impede one of the primary jobs of the immune system – preventing infection, and maybe even cancer.

Ideally, it would be better to find a treatment that "nicked" the specific part of the immune system that was causing the problem. If we could figure out which cells were involved in MS, that is, identify them as "biomarkers," we could make a more specific therapy that targeted just these cells – a "scalpel," rather than our current "sledgehammer." Eventually, we might be able to get so specific in identifying these cells and figuring out things like appropriate levels and relationships to other immune cells that we may even have different treatments for different people.

Dr. Steinman pointed out that we are making progress with neuromyelitis optica (NMO). We understand NMO better, and understand that aquaporin 4 (a protein in the brain and spinal cord) is the main antigen. It has been shown that blocking immune response to aquaporin 4 reduces NMO lesions. Dr. Steinman says that we need to put more effort into understanding these diseases that we have a better grasp of, as this will give us necessary clues to figuring out MS targets for treatment.

I'll paraphrase one presenter at ECTRIMS 2011 who talked about a "MS treatment Utopia" that would allow our neurologists to tell us exactly what kind of MS we had, what treatment would be best, how well it was working and exactly what to change to if it stopped working. Sounds like the next best thing to a cure.

This is my last blog from the ECTRIMS 2011 conference in Amsterdam. Thank you for reading these blogs. My goal was to bring you to the conference with me by giving you some highlights of the research presented. I will continue discussing more research findings on my site, ms.about.com, for many months to come. Check it out.

Keep coming back to this blog of the National MS Society. The Society is committed to keeping people with MS in the conversation and this is one way to get those of us with MS talking to scientists, researchers, doctors and each other.

Take care of yourselves, my friends.

2 comments:

  1. Julie,
    Thank you so so much. You and Marc Stecker (AKA The Wheelchair Kamikaze) are the best MS-to-understandable translators! Thanks also to the National MS Society, for this brilliant idea of having you reporting directly from ECTRIMS.
    I hope you can help me again getting permission to translate these precious contents to portuguese. Because the majority of MS conversations online are in english and not everyone understands...
    I work at the Portuguese MS Society and my dream is to change the MS faces in Portugal. I believe it is already happening, but there is so much more to do.
    All the best to you and have a safe and happy journey back home!
    Best wishes, Luísa Matias

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  2. I also want to thank you and NMSS for these informational blogs bringing the science down to a level I can understand, for the most part. I also follow your blog on about.com in addition to Trevis Gleason's Life with MS and you both deserve credit, along with the online MS communities and of course NMSS, in improving the quality of my life with MS, so Thank You!

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