The present proposal is to continue research based on the premises that small peptides of myelin basic protein originating from damaged central nervous system myelin enter cerebrospinal fluid, blood and urine of persons with multiple sclerosis and that measurement of these peptides offers a means of monitoring of tissue injury. These premises are based on results of previous investigations from a number of laboratories, including that of the applicant, that myelin basic protein-like material in cerebrospinal fluid is a valid laboratory index of myelin damage and disease activity in multiple sclerosis, and on the results of recent investigations from the applicant's laboratory demonstrating that MBP-like material is in urine and is probably in blood. Because of the varied and narrow immunochemical specificities of antibodies to the epitopes of small peptides of myelin basic protein, the ability to quantitate accurately the peptides of myelin basic protein depends on the specific identity of the peptides present and on the development of well-characterized antibodies and immunoassays for their detection. The present application is directed toward precisely characterizing the myelin basic protein- like material in cerebrospinal fluid and urine and toward new attempts to further define this material in blood. Accordingly, the specific aims of this study are: (1) To isolate and chemically identify by peptide sequence the myelin basic protein-like material in cerebrospinal fluid of patients with active multiple sclerosis and to contrast this with the myelin basic protein-like material in cerebrospinal fluid of multiple sclerosis patients in different phases of disease activity and in other neurological disease controls with myelin damage. (2) To perform similar characterization studies on the myelin basic protein-like material in the urine of multiple sclerosis and control patients. (3) To establish an enzyme-linked immunosorbent assay (ELISA) using monoclonal antibody to quantitate myelin basic protein-like material in body fluids; this technical aim is to improve consistency and feasibility of the immunoassay. (4) To further optimize the detection of myelin basic protein-like material in blood and to complete its chemical identification. (5) To monitor the level of cerebrospinal fluid, blood and urinary myelin basic protein-like material in multiple sclerosis patients during different phases of disease activity and during treatment with medications. The type and level of myelin basic protein peptide or peptides in human body fluids should be important indices for the therapeutic management of multiple sclerosis and may offer insight into the course or progression of the autoimmune response present in affected individuals.
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