The present proposal is based on the premise that small peptides of myelin basic protein originating from damaged central nervous system myelin can be detected in blood and urine of persons with multiple sclerosis. At the present time the measurement of basic protein or basic protein peptides in cerebrospinal fluid is the most reliable laboratory methodd for determining disease activity in multiple sclerosis. The detection and quantitation of basic protein peptides in blood or urine would permit a more feasible means for monitoring disease activity in multiple sclerosis. Given the narrow immunochemical specificities of antibodies to the epitopes of small peptides of basic protein, the ability to quantitate peptides of basic protein depends on the identification of the peptides present and on the development of immunoassays for them. Defining the nature of the basic protein-like material in cerebrospinal fluid and the specific basic protein peptides formed during clearance appears to be imperative for devising immunoassays capable of quantitating basic protein peptides in blood or urine. Accordingly, the specific aims of this study are: 1) to establish immunoassays for the detection and quantitation of fragments of basic protein peptide 43-88, notably those near the carboxyl terminal of this peptide and those formed by the degradation of basic protein peptide 43-88 by human renal proteinases, 2) to determine the molecular nature of the basic protein-like material present in the cerebrospinal fluid of persons with multiple sclerosis and 3) to utilize this information for examining blood and urine of multiple sclerosis patients for basic protein peptides. The type and the level of basic protein peptide or peptides in human body fluids shold be important indices for the therapeutic management of multiple sclerosis.
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