The ALS Association, Harvard Stem Cell Institute and Massachusetts General Hospital Neurological Clinical Research Institute are collaborating with GlaxoSmithKline on a clinical trial to evaluate the potential of an anti-epileptic drug in ALS patients. In parallel testing, brain cells will be made from each patient's stem cells to see if they can predict which patients might respond to the medicine.

The trial will evaluate the potential of the drug, Retigabine, which has a unique mechanism of action and can calm the excitability of nerve cells that are thought to cause seizures. These "hyperexcitable neurons" also are thought to play a role in ALS. Alongside testing of the medicine, scientists will for the first time create stem cells from these patients to see if they can be used to determine in advance which patients could benefit from the medicine.

The study is being led by Brian Wainger, M.D., Ph.D., of the department of neurology at Massachusetts General Hospital, in collaboration with Merit Cudkowicz, M.D., chief of neurology at MGH. It will be performed at 12 academic sites within the Northeast ALS Consortium, an international, independent, nonprofit group of researchers who collaboratively conduct clinical research in ALS and other motor neuron diseases. GSK will provide the drug, and funding support will come from HSCI, The ALS Association, the MGH NCRI and GSK.

"This novel study will provide us with a better understanding of neuron hyperexcitability, a potentially important disease mechanism in ALS patients," said Lucie Bruijn, Ph.D. MBA, chief scientist for the ALS Association. "This powerful collaboration of leaders in the fields of stem cells, clinical neurology, ALS research and GSK will be the first time that lab data from patient derived stem cells with disease-specific properties that respond to drugs have formed the basis for a clinical trial. It is our hope that this novel approach demonstrates promising results and leads to better clinical trials for ALS patients in the future."

Amyotrophic lateral sclerosis, or ALS, is a progressive neurodegenerative disease that affects nerve cells (neurons) in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. There is no cure, and there are no life-prolonging treatments for the disease.

A large body of data supports the hypothesis that neurons become hyperexcitable in ALS, firing more than they normally do. Such overactivity may contribute to the death of the nerve cells, considered a root cause of the disease. In cell models of ALS, Retigabine has shown the ability to reduce excitability and prolong survival in the lab.

Preclinical work leading up to this study was performed at Boston Children's Hospital and Harvard University. Stem cell modeling development was supported by Project ALS and NINDS with identification of Retigabine as a target supported by Target ALS, ALS Association, Harvard NeuroDiscovery Center, American Brain Foundation and NINDS.

In this collaborative study, researchers will test whether Retigabine can reduce excitability of upper and lower motor neurons. The study will include non-invasive measurements of nerve cells and nerve function as biomarkers of the effect of the drug. In addition, blood cells from treated subjects will be isolated and studied using stem cell technology to uncover cellular determinants of drug response. This is the first time that this technology has been applied in a clinical trial and could open up new possibilities for drug research and development.