News Release

Ezogabine treatment shown to reduce motor neuron excitability in ALS patients

Mass. General investigator presented initial clinical trial results at Motor Neurone Disease Association meeting

Peer-Reviewed Publication

Massachusetts General Hospital

Brian Wainger, MD, PhD, of the Healey Center for ALS at Massachusetts General Hospital (MGH) presented initial, top-level results of a recently completed phase 2 clinical trial of ezogabine (also called retigabine) on December 9 at the Motor Neurone Disease Association annual meeting in Glasgow, Scotland. The trial met its primary goal of measuring a reduction in motor neuron excitability in people with amyotrophic lateral sclerosis (ALS) following treatment.

ALS - also called Lou Gehrig's disease or motor neuron disease - is a progressive neurodegenerative disorder that leads to the death of neurons in the brain and spinal cord. There are only three drugs with limited effects approved in the United States for treating ALS, and new therapies that substantially prolong lifespan are urgently needed. An essential step toward developing new treatment avenues is unraveling the biological processes that go awry in this disorder and identifying novel molecular targets for drug intervention.

Ezogabine has a unique mechanism of action of activating the Kv7 or KCNQ family of voltage-gated potassium channels in cell membranes and can calm the excitability of nerve cells that cause seizures. Similar "hyperexcitability" in motor neurons may play a role in ALS, and the study - conducted by investigators from the MGH Neurological Clinical Research Institute (NCRI) at sites of the Northeast ALS Consortium - evaluated ezogabine's potential in the context of ALS. The investigators used transcranial magnetic stimulation and threshold tracking nerve conduction studies to measure the effects of ezogabine on upper and lower motor neuron excitability in 65 people with ALS and found that treatment did reduce motor neuron excitability. The study was not powered to assess clinical outcomes.

This trial was supported by The ALS Association, GlaxoSmithKline, the Harvard Stem Cell Institute (HSCI) and the MGH NCRI. Preclinical studies in human induced pluripotent stem cells (iPSCs) leading up to the clinical trial, performed at Boston Children's Hospital and Harvard University, were supported by The ALS Association, HSCI, the National Institute of Neurological Disorders and Stroke, the New York Stem Cell Foundation and Target ALS. Wainger is a New York Stem Cell Foundation - Robertson Investigator.

"This novel study provides us with a better understanding of neuron hyperexcitability, an important ALS disease pathway, and we are thrilled to be a part of such a powerful collaborative team," says Calaneet Balas, president and CEO of The ALS Association.

Lucie Bruijn, PhD, MBA, chief scientist, The ALS Association, adds, "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."


The mission of the Neurological Clinical Research Institute at MGH is to accelerate translational research in neurological disorders through initiating and testing novel therapies. In collaboration with investigators in the recently established Healey Center for ALS at Mass General, directed by Merit Cudkowicz, MD, MSc, chief of Neurology, the NCRI faculty and staff develop, design, support and manage innovative observational and interventional trials for neurological disorders. The NCRI is also the clinical coordination center for the National Institute of Neurological Disorders and Stroke-supported NeuroNEXT phase 2 trial network and both the coordinating center and a clinical research site for the Northeast ALS Consortium, a network of ALS specialists at more than 120 locations worldwide.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $900 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, genomic medicine, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, photomedicine and transplantation biology. The MGH topped the 2015 Nature Index list of health care organizations publishing in leading scientific journals and earned the prestigious 2015 Foster G. McGaw Prize for Excellence in Community Service. In August 2018 the MGH was once again named to the Honor Roll in the U.S. News & World Report list of "America's Best Hospitals."

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