Issues in multiple sclerosis. A focused disease oriented research program.

Abstract

This report presents a brief overview of our own focused disease oriented research program, and rationale, to find the etiopathogenesis of multiple sclerosis (MS). Our hypothesis-driven research proposes that MS is caused by a persistent virus located at the edge of active plaques. Further, we propose that the immune system has eradicated the virus from inactive plaques or that the putative virus has become latent. In 1988 polymerase chain reaction (PCR) was reported and it has turned out to be the most sensitive and specific method to detect viral nucleic acid sequences in body fluids and tissues. This technique may be a breakthrough to test the MS viral hypothesis. Our search is further enhanced by the availability of a large collection (from MS Neurospecimen Bank) of cryopreserved MS brains and other neurological diseases suitable for PCR. An enigma is the specificity of the elevation of intrathecal IgG synthesis (rate and oligoclonal bands) that is found in over 99% of clinically definite MS cases. Our 2 dimensional electrophoresis of cerebrospinal fluid (CSF) IgG shows it to be temporally and clonally stable, evidence that intrathecal IgG synthesis is not non-specific. Intrathecal IgG synthesis is a marker of IgG synthesizing plasma cells in the central nervous system (CNS) and especially in active plaques. Another issue is the inclusion in all clinical trials of our objective quantitative examination of neurologic function (instrumented tests of functions which patients want improved) as well as CSF examination before and after the trial to determine the effect of the putative treatment on the polyphasic CNS inflammation.