Targeting immunotherapy in multiple sclerosis

After years of limited success treating MS with nonspecific immunosuppressants and corticosteroids, improved understanding of the complex immune-mediated disease process has begun to suggest more specific treatment approaches.1 In this issue of Neurology, clinical trials using two new treatment approaches are reported: 1) blocking adhesion molecules, receptors that promote leukocyte entry into inflamed tissues2; and 2) decreasing activity of tumor necrosis factor-alpha (TNFα), a proinflammatory cytokine.3 As described by the investigators, preclinical laboratory and animal studies provide extensive evidence that both of these treatments might reduce disease activity in MS. These were the first studies examining their safety and potential efficacy in patients, using serial MRI scans as the primary measure of their effects on disease activity.

In the randomized, double-blind, placebo-controlled study of humanized anti-α4β1 integrin monoclonal antibody (Antegren, “a near hit”3), Tubridy et al. demonstrated that Antegren is well tolerated and reduced the number of active (new, enlarging, or enhancing) MRI lesions in 72 patients with relapsing and secondary progressive MS for the first 12 weeks after initiating therapy. This observation establishes “proof-of-concept,” suggesting that blocking adhesion molecules in general, and Antegren specifically, may prove to have a meaningful therapeutic effect in MS patients. The size of the treatment effect was modest, however (as shown in figure 1 in their article), and was confined to the first 12 weeks of the study. Furthermore, the duration of enhancement …