Myasthenia gravis, a chronic autoimmune neuromuscular disease, is characterized by muscle weakness that increases during periods of activity and improves after periods of rest and can result in life-threatening complications such as respiratory failure. Often patients present with weakness confined to the ocular muscles, Ocular Myasthenia Gravis but within 1 to 2 years, approximately two-thirds of patients develop generalized disease. This application is for funding to support the final planning of a clinical trial for patients with Ocular Myasthenia Gravis. A double masked, placebo-controlled, randomized clinical trial of 240 patients will be designed to test the hypothesis that corticosteroid therapy with prednisone, in doses that do not cause major adverse events or side effects, will reduce the incidence of systemic muscle involvement and improve disease-related visual disability at one year. Reducing the risk of Generalized Myasthenia Gravis will decrease the risk of overall disability, Myasthenic crises, hospitalizations, and costly invasive therapies such as thymectomy and plasmaphoresis. In addition, if the proposed therapy reduces double vision and restores binocular function, patients may be better able to perform activities of daily living such as reading, driving an automobile, handling machinery, and work. If chronic low dose corticosteroids are beneficial in decreasing the incidence of generalized disease as well as reducing visual disability, it will replace the moderate to high dose therapy used by many neurologists; there by avoiding the significant complications of hypertension, infections, hyperglycemia, and osteoporosis. Our activities during the one year award period will be directed towards developing a Manual of Procedures, finalizing Study protocol, recruiting clinic sites, outlining data management systems, detailing Study drug distribution and tracking, creating clinic and patient brochures, and preparing and submitting the grant applications for the Study trial, via executive committee meetings and teleconferences.
