Vaccine offering potential cure for rare autoimmune disorder Myasthenia Gravis.
Myasthenia gravis (MG) is caused by an antibody-mediated autoimmune response to muscle nicotinic acetylcholine receptors (AChRs) of skeletal muscles that impairs neuromuscular transmission, resulting in weakness and fatigability. The prevalence in the U.S. is estimated at 20 cases per 100,000 people. The cause for the autoimmune response to AChRs in MG is not known.
Current treatment options include acetylcholinesterase inhibitors (with modest efficacy at improving neurotransmission) and nonspecific immunosuppressants (whose beneficial effects may be delayed for up to 18 months and can cause severe side effects). No specific immunosuppressive therapy is available.
Dr. Jon Lindstrom and his team at Penn have developed a specific immunosuppressive therapy with great potential for treating MG. The vaccine utilizes cytoplasmic domains of human AChR subunits and incomplete Freund’s adjuvant.
When tested in rat models of the experimental autoimmune myasthenia gravis (EAMG), which is considered the gold standard animal model for MG, the vaccine was demonstrated to be a safe and rapidly suppressed established chronic EAMG providing long-term, possibly permanent, resistance to re-induction of EAMG. The next planned steps are to optimize dose and schedule with an adjuvant such as alum that can be used in humans and test the vaccine in cats with naturally occurring MG.
- long-lasting benefits, potentially permanent protection
- potent, safe, and rapidly acting
- prevention as well as reversal of chronic MG
- potential veterinary use (cats, dogs and other animals can be affected by MG)
Stage of Development:
In vivo data including data on dose and treatment paradigms
Luo J and Lindstrom J (2014) Antigen-specific immunotherapeutic vaccine for experimental autoimmune myasthenia gravis. J Immunology 193: 5044-5055
Jon Lindstrom, Ph.D. is a world-renowned expert studying acetyl choline receptors for over 40 years. Dr. Lindstrom was first to purify AChR from fish electric organs which led to his discovery that MG is caused by an antibody-mediated autoimmune response to muscle AChRs. Along with collaborators, Dr. Lindstrom discovered the pathological mechanisms by which autoantibodies to AChRs impair neuromuscular transmission in MG and its animal model. He has developed monoclonal antibodies to the subunits of muscle and neuronal AChRs which are used by researchers throughout the world. He also developed the immunodiagnostic assay for MG. The Lindstrom lab has the reagents, animal models, and expertise to further develop the technology in lab settings as well as has access to the MG patients at the UPenn hospitals.
Docket # 15-7271