Treatment of Lambert-Eaton Myasthenic Syndrome

Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disorder with a basis in abnormal interaction between nerve cells and muscles due to overproduction and accumulation of antibodies that block communication signals. The antibodies against the voltage‐gated calcium channels that provide the calcium ion flux that triggers acetylcholine release at the neuromuscular junction lead to the symptoms of the syndrome. LEMS can affect many muscles, but usually it causes weakness primarily in the upper legs and hips, although it can also affect the upper arms and shoulders. LEMS can also affect muscles in the eyelids, causing drooping eyelids, and it can even sometimes affect muscles that move the eyes, resulting in mild double vision, In a few instances, weakness in the muscles of the face develops and that can affect chewing, swallowing, and breathing. Involvement of the autonomic nervous system is also likely and may cause a dry mouth; It is notable that about half of patients with LEMS have or will develop cancer, especially small cell lung cancer. LEMS is often misdiagnosed as myasthenia gravis (MG), inclusion body myositis, Guillain-Barré syndrome (GBS), amyotrophic lateral sclerosis (ALS), lumbar canal stenosis, early-phase Parkinson's disease and lower body parkinsonism. The prevalence of LEMS is estimated to be between 1/250,000- 1/333,300 worldwide.

Firdapse (3,4-Diaminopyridine, 34DAP) is a drug approved in Europe for the treatment of LEMS. The manufacturer is seeking U.S. approval for LEMS after obtaining that approval in Europe. U834 is a new drug developed in our group at the University of Kentucky College of Pharmacy for the treatment of LEMS. It appears to offer superior efficacy with fewer side effects.