Randomized study of antibodies to IFN-gamma and TNF-alpha in secondary progressive multiple sclerosis

Studies of cytokines in multiple sclerosis (MS) have shown that immune mechanisms connected with disturbance of the synthesis of cytokines probably play critical roles in the initiation and prolongation of MS. In a double-blind, placebo-controlled trial, 45 patients with active secondary progressive MS were randomized to three groups of 15 patients, each receiving a short course of antibodies to IFN-gamma, to tumor necrosis factor (TNF)-alpha, or a placebo. After 12 months with analysis of disability (Expanded Disability Status Scale scores), accompanied by interval determinations of lymphocyte subpopulations, cytokine production levels, MRI, and evoked potentials, it was found that only patients who received antibodies to IFN-gamma showed statistically significant improvement compared to the placebo group--a significant increase in the number of patients without confirmed disability progression. This was supported by MRI data (a decrease in the number of active lesions) and systemic changes in cytokine status (a decrease in IL-1beta, TNF-alpha, and IFN-gamma concentrations in supernatants of actvated blood cells of these MS patients and an increase in TGF-beta production). Neutralization of IFN-gamma could be a new approach to treating secondary progressive MS. Long-term administration of humanized monoclonal antibodies to IFN-gamma and simultaneous use of antibodies to IFN-gamma together with IFN-beta products are planned.