Lambert-Eaton Myasthenic Syndrome (LEMS)

Research

Although there is an FDA-approved therapy for Lambert-Eaton myasthenic syndrome (LEMS) — Firdapse (a potassium channel blocker) — research continues into developing effective next-generation LEMS therapies.

There have been several important advances in LEMS research in the last few years. In a recent interview with MDA, Stephen Meriney, PhD, professor in the Department of Neuroscience and co-director of the Center for Neuroscience Graduate Program at the University of Pittsburgh, gave an overview of the state of LEMS research in 2019.

According to Meriney, recent advances include:

• Identifying diagnostic criteria that can predict lung cancer risk for LEMS patients
• Reports that LEMS may improve small cell lung cancer prognosis
• Development of new calcium channel gating modifiers

In addition to these advances, clinical studies of LEMS patients are ongoing to advance scientific understanding of disease progression and how LEMS associates with cancer. Studies are being conducted that use a LEMS mouse model to understand in greater detail how LEMS antibodies alter acetylcholine release. Additionally, further refinement and preclinical testing of new calcium channel modifiers is ongoing.

One new treatment in preclinical development is a small molecule that holds calcium channels open longer. In animal studies, when this calcium channel modifier is combined with 3,4-diaminopyridine (3,4-DAP), the magnitude of acetylcholine release in LEMS-model mice can be completely restored to normal levels. This combination therapy approach has the potential to be a next-generation treatment for LEMS and related conditions with reduced neurotransmitter release, but further research in human patients is needed.