New hope for primary progressive multiple sclerosis?

Multiple sclerosis is generally classified into three forms. The relapsing-remitting form is the most common initial form. It is characterized by periods when the symptoms get much worse separated by periods where they get better. The second form is the primary progressive form where the symptoms slowly and steadily get worse. It is generally thought to have a worse prognosis than the relapsing-remitting form. In many cases the relapsing-remitting form converts to a progressive form at some time. This is then the secondary progressive form. In the meantime there is a big variety of drugs on the market which are approved for the treatment of the RR form of MS. They cannot stop the disease but they can slow its progression. Until very recently there was no drug approved for the treatment of progressive MS. This has now changed with the approval of ocrelizumab, an antibody against the molecule CD20 which is found on the surface of B cells. It has been approved for both the RR form and some cases of the progressive form of MS.

Ocrelizumab acts by causing B cells to be killed. It has been seen to have strong positive effects in combatting MS in some cases. This emphasizes the fact that T cells, usually regarded as the main culprit causing damage during MS, are not alone. B cells also seem to play an important role although what role that is is not so clear. There previously existed an antibody against CD20, rituximab, which was used in the therapy of diseases other than MS. Ocrelizumab has had problemtic side effects, with a high frequency of infections and a slightly increased cancer risk. For this reason it has been abandoned as a therapy for rheumatoid arthritis. On the other hand the trial for MS has less problems with side effects.

One reason not to be too euphoric about this first treatment for progressive MS is the following. It has been shown to be effective against patients in the first few years of illness and those where there are clear signs of inflammatory activity in MRT scans. This suggests to me a certain suspicion. The different types of MS are not clearly demarcated. Strong activity in the MRT is typical of the RR form. So I wonder if the patients where this drug is effective are perhaps individuals with an atypical RR form where the disease activity just does not cross the threshold to becoming manifest on the symptomatic level for a certain time. This says nothing against the usefuleness of the drug in this class of patients but it might be a sign that its applicability will not extend to a wider class of patients with the progressive form in the future. It also suggests caution in hoping that the role of B cells in this therapy might help to understand the mechanism of progressive MS.

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