Although myasthenia gravis (MG) is the best characterized human autoimmune disease, no cure is available. Antibodies to nicotinic acetylcholine receptors (AChRs) of muscle are detectable in 90 percent of patients and cause the weakness of MG. Antibody levels can be decreased by plasmapheresis, and this is correlated with improved clinical status. This research will establish the feasibility of developing an antigen-specific immunoadsorption device to remove anti-AChR in MG. Toward this goal, Applied ImmuneSciences, Inc., has recently designed, cloned, and expressed the major extracellular domain (amino acid residues 1-210) of the a subunit of human AChR.The specific aims are: (1) purification of recombinant AChR (rAChR) from Escherichia coli by conventional and affinity chromatographic techniques, (2) characterization of rAChR by physical and biological techniques, (3) covalent immobilization of rAChR onto cellulosic membranes, and (4) evaluation of the efficacy of immobilized rAChR for specific removal of pathologic antibody from MG patient sera using a combination of immunoassays.Development of an antigen-specific immunoadsorption device represents a significant advance in the treatment of MG because it will allow for the safe and effective removal of MG patient autoantibodies. In conjunction with specific T-cell therapy, there is now hope for antigen-specific immunomodulations that may even lead to a longterm cure.Awardee's statement of the potential commercial applications of the research:This research project will accomplish feasibility studies for an antigen-specific immunoadsorption device. This should improve the treatment of patients with MG and may help in developing methods to induce a long-term cure of this disease.National Institute of Neurological Disorders and Stroke (NINDS)
