Surrogate Markers for MS

Fred D. Lublin, MD: I do want to correct 1 thing. The presence of oligoclonal bands is not a surrogate for a dissemination in time, it’s instead of time. Because there is no time element. And one of the things that I’ve never been able to get an answer to is, when in the course of MS [multiple sclerosis] do the oligoclonal bands appear? And If you start very early, in these very early cases, might they not be there yet? Do you have a concept for that?

Patricia K. Coyle, MD: Well, I think they’ve had data. Over time, the oligoclonal band positivity rate gets higher and higher, to 95% plus. And one of the things about MS oligoclonal bands is they do not spontaneously go away, as opposed to other disorders. At the first attack you can have an expectation of close to 80% being positive with a sensitive assay.

Fred D. Lublin, MD: Suhayl, what about neurofilament light [NFL] or any other markers?

Suhayl S. Dhib-Jalbut, MD: So neurofilament is a skeletal protein that is elevated in the spinal fluid of patients with a variety of neurodegenerative diseases, not just MS. It’s elevated in Alzheimer disease, in stroke, and probably Parkinson disease as well. So in that regard it is not really specific for MS. Studies have shown that it is increased as the disease progresses. And more recently we know that it is also increased as a result of an acute relapse. We also now know that it responds to treatment. A variety of studies have shown, with the different immunomodulatory medications we have now, that the level of NFL goes down as a result of treatment. I think the main advance is that we can now measure it in the serum with more sensitive technique instead of having to do a spinal tap.

I think the big question is, will it be validated as a surrogate marker of damage and disease progression? I think we are not there. It needs to be validated, for example, against atrophy studies by MRI [magnetic resonance imaging], because it has the potential to be used as a surrogate marker in clinical trials. There’s also some data that say that at the onset of MS, if NFL levels are very high, that is a predictor of first prognosis. So maybe a combination of biomarkers such as oligoclonal bands and NFL level at the time of diagnosis, together, might be better a predictor of prognosis.

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