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Issues in multiple sclerosis. A focused disease oriented research program
1Neurology Service, VAMC W. Los Angeles, California.
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.
Insights
This research investigates the viral cause of multiple sclerosis (MS), proposing a persistent virus in active lesions. Advanced polymerase chain reaction (PCR) techniques and cerebrospinal fluid (CSF) analysis are key to testing this hypothesis.
Area of Science:
- Neuroimmunology
- Virology
- Neurology
Background:
- Multiple sclerosis (MS) etiopathogenesis remains incompletely understood.
- A persistent viral infection is hypothesized as a potential cause of MS.
- Intrathecal IgG synthesis, including oligoclonal bands, is a hallmark in most MS cases.
Purpose of the Study:
- To investigate the hypothesis that MS is caused by a persistent virus.
- To explore the role of viral nucleic acid detection using polymerase chain reaction (PCR).
- To analyze the specificity and stability of intrathecal IgG synthesis in MS.
Main Methods:
- Utilizing polymerase chain reaction (PCR) to detect viral nucleic acid sequences in MS neurospecimens.
- Analyzing cryopreserved brain tissue from the MS Neurospecimen Bank.
- Employing 2D electrophoresis of cerebrospinal fluid (CSF) IgG to assess intrathecal synthesis.
- Incorporating objective quantitative examination of neurological function in clinical trials.
Main Results:
- The study highlights the potential of PCR as a sensitive method for detecting viral sequences relevant to MS.
- 2D electrophoresis indicates that intrathecal IgG synthesis in MS is temporally and clonally stable.
- Elevated intrathecal IgG synthesis is a specific marker associated with active plaques in the central nervous system (CNS).
Conclusions:
- The research proposes a viral hypothesis for MS etiopathogenesis.
- Advanced molecular techniques like PCR are crucial for investigating this hypothesis.
- Understanding intrathecal IgG synthesis provides insights into CNS inflammation in MS.