Brian Wainger, MD, PhD: Future Studies Evaluating Motor Neuron Excitability in ALS

January 11, 2021
Brian Wainger, MD, PhD

Assistant professor in anesthesiology and neurology, Harvard Medical School; and attending physician, Massachusetts General Hospital

The assistant professor of neurology and anesthesiology at Harvard Medical School detailed the future outlook of ezogabine and whether it may be studied again in patients with ALS.

"I’m hoping that it sets this paradigm for repurposing drugs quickly from stem cell work to patients and having confidence that the stem cell models can be predictive. For me, that’s the big value.”

Ezogabine, once FDA-approved as an adjunctive therapy for partial-onset seizures uncontrolled by medications in patients with epilepsy, was recently found to decrease cortical and spinal motor neuron (MN) excitability in patients with amyotrophic lateral sclerosis (ALS) in a phase 2 randomized controlled trial. Despite the drug not showing any changes in cognition or slowing progression of the disease, researchers suggested that the MN excitability may be used as a pharmacodynamic biomarker in future clinical studies.

Spinal MN axonal hyperexcitability, which has been indicated by strength-duration time constant (SDTC) measured using threshold tracking nerve conduction studies (TTNCSs) has been previously found in patients with sporadic and familial ALS, according to study authors Brian Wainger, MD, PhD, and his colleagues. The additional TTNCS parameters of depolarizing threshold electrotonus, super-excitability, and latency were all affected with ezogabine treatment.

Wainger claims that he and his colleagues were not disappointed by the lack of effect ezogabine had on survival functions, but were content that it was able to show a proof of mechanism for opening this particular potassium channel and potassium channels in general. He sat down with NeurologyLive to provide details on the potential next steps of ezogabine, how clinicians can build off the data observed, and whether a phase 3 trial would be on the way.