Promising Results Published on a New ALS Drug Discovered with NYSCF Support

Ezogabine (an epilepsy drug), has successfully reduced a hallmark of ALS in 65 patients participating in a phase 2 clinical trial, according to a recent report in JAMA Neurology. The drug was initially discovered using a NYSCF-funded stem cell model, and this is the first ALS clinical trial to test a finding made possible through stem cells. 

The work is the result of a collaboration between Brian Wainger, MD, PhD (a NYSCF – Robertson Stem Cell Investigator, Assistant Professor of Neurology and Anesthesiology at Harvard Medical School, and a physician at Massachusetts General Hospital) and NYSCF Senior Scientific Advisor Kevin Eggan, PhD (Group Vice President and Head of Research and Early Development at BioMarin Pharmaceutical and a Professor at Harvard University, Director of Stem Cell Biology for the Stanley Center for Psychiatric Research at the Broad Institute, and an Institute Member of the Broad Institute of MIT and Harvard).

A few years ago, with induced pluripotent stem cell (iPSC) models of ALS, Dr. Eggan discovered that in the disease, motor neurons (the cells that tell our muscles to move) tended to show a lot of electrical activity, causing them to essentially die of exhaustion. Dr. Wainger, a colleague of Dr. Eggan’s, happened to know of a drug called ezogabine (or retigabine) that addresses this very same problem in a different disease: epilepsy.

Stem cell models of ALS showed that ezogabine could effectively quell overactive motor neurons in a dish, and the team soon embarked on a clinical trial to test the drug in patients. Because the drug was already FDA approved, it was able to bypass the mouse studies that typically precede clinical trials and instead move quickly to patient use. 

The results of the trial, which recently concluded Phase 2, indicate that ezogabine is effective and has reduced motor neuron excitability in 65 ALS patients. The team next plans to see whether longer treatment can sustain the drug’s benefits and perhaps slow disease progression.