In this interdisciplinary program project grant, we are combining the clinical and research expertise of 25 persons. All have an appointment in the Department of Neurology at Johns Hopkins, but their expertise also includes the areas of clinical neurology, veterinary medicine, neuropatholgy, neurovirology, neuroimmunology, neurochemistry, and basic neurobiology. This is not a proposal directed at specific disease entity. Studies of maintenance of neural integrity, maintenance of normal transmission, and response of neural elements in repair and regeneration cross disease lines. Virological and immunological studies, which are directly related to inflammatory diseases, are also relevant to multiple sclerosis, amyotrophic lateral sclerosis, and myasthenia gravis where viruses or abnormal immune responses have been suggested as etiologies. Similarly, the understanding of the selective vulnerability and unique responses of specific cell types to intrinsically and extrinsically derived pathologies may provide knowledge about disease detection, activity, and therapy. The majority of the investigators in this proposal are, however, clinical neurologists, and seek to apply knowledge in the basic neurosciences to human disease. For example, our previous work has led to detection of myeline basic protein in cerebrospinal fluid in multiple sclerosis, demonstration of abnormal acetylcholine receptors and circulating antibody to the acetylcholine receptor in myasthenia gravis, and antigenic shift as a possible mechanism of recurrent viral infection. The areas of proposed investigation include characterization of isolated neurons, effects of denervation of neurons, response of specific cell types to viral infection, cellular host mechansims to viral infections, alteration of anterior horn cell in a genetic model of ALS, abnormalities of axonal flow in models of peripheral neuropathy, membrane abnormalities in models of muscle disease, and clinical projects relating to detection and immune abnormalities in multiple sclerosis and pathogenesis and treatment of myasthenia gravis.
