NYSCF-Supported Research Leads to Successful Phase 2 Clinical Trial for ALS

An epilepsy drug, initially tested using a stem cell model of ALS developed with NYSCF support, has successfully reduced motor neuron excitability (a hallmark of the disease) in 65 ALS patients participating in a phase 2 clinical trial. Brian Wainger, MD, PhD (a NYSCF – Robertson Stem Cell Investigator, Assistant Professor of Neurology and Anesthesiology at Harvard Medical School, and physician at Massachusetts General Hospital) presented the results of the trial at the Motor Neurone Disease Association annual meeting in Glasgow, Scotland this week.

ALS is a neurodegenerative disorder that affects motor neurons (the cells that tell our muscles to move), leading to severe muscle weakness and dysfunction. The lab of NYSCF Senior Scientific Advisor Kevin Eggan, PhD, was the first to use stem cells to create a model of ALS (another NYSCF-funded endeavor) that could be used to characterize aspects of the disease. A few years ago, with induced pluripotent stem cell (iPSC) models of ALS, Dr. Eggan discovered that in the disease, motor neurons 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 that addresses this very same problem in a different disease: epilepsy.

This realization motivated Drs. Wainger and Eggan to start a clinical trial testing the drug—called ezogabine (or retigabine)—in ALS patients. Shown to be effective on stem cell models of the disease (and already approved as safe by the FDA), this drug was able to bypass the mouse studies that typically precede clinical trials and instead move quickly to patient use. In his talk on Sunday, Dr. Wainger reported that Ezogabine has been working— it successfully reduced motor neuron excitability in 65 ALS patients.

This trial is an important demonstration of how stem cell models can be used to accelerate drug discovery.

“This is the first clinical trial for ALS that was designed using data based on an iPSC model of ALS and was possible in part due to the availability of a biomarker in people living with disease that measures excitability of motor neurons, also characterized in the iPSC model,” said Lucie Bruijn, PhD, MBA, chief scientist, The ALS Association.

Moving treatments out of the lab and into the clinic is NYSCF’s ultimate goal, and we look forward to supporting further studies that leverage the power of stem cells to make this possible.