November 22, 2002

George receives Javits Award to further epilepsy research

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Graduate student Chris Lossin and Dr. Al George examine how mutations in proteins called sodium channels contribute to human diseases and disorders. George received a Javits Investigator Award to support studies of inherited epilepsy. (photo by Anne Rayner Pollo).

George receives Javits Award to further epilepsy research

Dr. Alfred L. George Jr., Grant W. Liddle Professor of Medicine and Pharmacology, has received a Javits Investigator Award from the National Institute of Neurological Disorders and Stroke. The award, named for the late Sen. Jacob Javits of New York, provides up to seven years of continuous funding to investigators who “have a distinguished record of substantial contributions in a field of neurological science.”

“I am delighted, of course,” said George, who also is director of the division of Genetic Medicine. “One of my postdoctoral mentors had a Javits Award, and I remember thinking that it seemed like an unobtainable goal.”

The NINDS chooses Javits Award recipients from among those investigators submitting regular research grant applications for competitive review. George received the award for his longest-running grant — first awarded in 1993 — which focuses on hereditary defects in human sodium channels. During the nine years of grant support, he and colleagues have published more than 50 peer-reviewed articles related to sodium channel disorders.

Sodium channels are donut-like pores embedded in the cell membrane that let electric current — in the form of sodium ions — flow into the cell. They play particularly important roles in electrically excitable tissues like the brain, heart, and muscle.

George and colleagues have studied sodium channel mutations associated with diseases in each of these tissues. In the initial years of grant support, they focused on inherited muscle diseases like hyperkalemic periodic paralysis, then changed gears, George said, and began studying inherited cardiac arrhythmias. Most recently, they have added inherited epilepsies to the repertoire of disorders under investigation in the laboratory.

The Javits Investigator Award will support the group’s ongoing efforts to understand how sodium channel mutations contribute to epilepsy, a disorder that affects more than 2 million Americans.

Earlier this year, George and colleagues reported in the journal Neuron how certain sodium channel mutations perturb the electrical properties of brain cells, findings that supported a plausible mechanism for epilepsy. With the Javits funding, they will continue to define brain sodium channel mutations in different epilepsies, George said, and to characterize both the functional and pharmacologic properties of the altered channels.

“It may be possible, in cases where there’s abnormal sodium channel function, to find anticonvulsant drugs or other drugs that selectively suppress that abnormal activity,” he said.

If abnormal sodium channel activity is contributing to epileptic seizures, then drugs that block the abnormal activity might be useful for treating epilepsy, and perhaps also for preventing it from developing in the first place. One theory holds that a sodium channel defect makes an individual more susceptible to having seizures, and that the seizures themselves then cause neuronal damage and create a focal point for future seizures.

“Preventing the damage could be an important issue, and perhaps someone known to have a sodium channel mutation should be on a prophylactic anticonvulsant — the right anticonvulsant,” George said.

The Javits Investigator Awards are part of a category of NIH grants called MERIT (Method to Extend Research In Time) awards.

“One of the purposes of MERIT awards is to give investigators a little more freedom to pursue more risky experiments,” George said. “I’m already thinking about what we can do with the extra time and the extra funding to make a more significant advance.”