Multiple Sclerosis,
October 2001,
vol. 7, no. 5, pp. 277-284(8)
Skurkovich S. [1] *; Boiko A. [2];
Beliaeva I. [2]; Buglak A. [2]; Alekseeva T. [2]; Smirnova N. [2]; Kulakova
O. [3]; Tchechonin V. [4]; Gurova O. [4]; Deomina T. [2]; Favorova O.O.
[3]; Skurkovich B. [5]; Gusev E. [2]
[1] Advanced Biotherapy Laboratories,
Rockville, MD, USA
[2] Department of Neurology and
Neurosurgery, Russian State Medical University, Moscow, Russia
[3] Department of Molecular Biology
and Biotechnology, Russian State Medical University, Moscow, Russia
[4] Immunochemical Laboratory of
the Russian State Scientific Center of Social and Legal Psychiatry, Moscow,
Russia
[5] Brown University Medical Center,
Providence, Rhode Island, USA
[*] Correspondence: S Skurkovich,
802 Rollins Avenue, Rockville, MD 20852 USA
Abstract:
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.
© 2001 ingenta