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Randomized study of antibodies to IFN-g and TNF-a in secondary progressive multiple sclerosis

Advanced Biotherapy Laboratories, Rockville, MD, USA

A Boiko

Department of Neurology and Neurosurgery, Russian State Medical University, Moscow, Russia

I Beliaeva

Department of Neurology and Neurosurgery, Russian State Medical University, Moscow, Russia

A Buglak

Department of Neurology and Neurosurgery, Russian State Medical University, Moscow, Russia

T Alekseeva

Department of Neurology and Neurosurgery, Russian State Medical University, Moscow, Russia

N Smirnova

Department of Neurology and Neurosurgery, Russian State Medical University, Moscow, Russia

O Kulakova

Department of Molecular Biology and Biotechnology, Russian State Medical University, Moscow, Russia

V Tchechonin

Immunochemical Laboratory of the Russian State Scientific Center of Social and Legal Psychiatry, Moscow, Russia

O Gurova

Immunochemical Laboratory of the Russian State Scientific Center of Social and Legal Psychiatry, Moscow, Russia

T Deomina

Department of Neurology and Neurosurgery, Russian State Medical University, Moscow, Russia

O O Favorova

Department of Molecular Biology and Biotechnology, Russian State Medical University, Moscow, Russia

B Skurkovich

Advanced Biotherapy Laboratories, Rockville, MD, USA, Brown University Medical Center, Providence, Rhode Island, USA

E Gusev

Department of Neurology and Neurosurgery, Russian State Medical University, Moscow, Russia

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-g, to tumor necrosis factor (TNF)-a, 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-g 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-1b, TNF-a, and IFN-g concentrations in supernatants of activated blood cells of these MS patients and an increase in TGF-b production). Neutralization of IFN-g could be a new approach to treating secondary progressive MS. Long-term administration of humanized monoclonal antibodies to IFN-g and simultaneous use of antibodies to IFN-g together with IFN-b products are planned.

Key Words: multiple sclerosis • anti-interferon- • anti-tumor necrosis factor- • cytokines

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