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Antibiotics protect nerves in mice by turning on genes

A family of antibiotics that includes penicillin may help prevent nerve damage and death in a wide variety of neurological diseases, including Lou Gehrig's disease, dementia, stroke, and epilepsy, Johns Hopkins researchers have found.

The antibiotics' beneficial effects, discovered in experiments in the lab and with mice, are unrelated to their ability to kill bacteria, the researchers report in the Jan. 6 issue of Nature. Instead, the drugs squelch the dangerous side of a brain chemical called glutamate by turning on at least one gene, thereby increasing the number of "highways," or transporters, that remove glutamate from nerves.

"It would be extremely premature for patients to ask for or take antibiotics on their own," says the study's leader, Jeffrey Rothstein, M.D., Ph.D., director of the Robert Packard Center for ALS Research at Johns Hopkins and a professor of neurology and of neuroscience. "Only a clinical trial can prove whether one of these antibiotics can help and is safe if taken for a long time."

In mice engineered to develop the equivalent of Lou Gehrig's disease, daily injections of an antibiotic called ceftriaxone, started just as symptoms tend to surface, delayed both nerve damage and symptoms and extended survival by 10 days compared to untreated animals. Lou Gehrig's disease, or amyotrophic lateral sclerosis (ALS), in people causes progressive weakness and paralysis and ends in death, usually within three to five years of diagnosis.

"We're very excited by these drugs' abilities," says Rothstein. "They show for the first time that drugs, not just genetic engineering, can increase numbers of specific transporters in brain cells. Because we study ALS, we tested the drugs in a mouse model of that disease, but this is much bigger than ALS. This approach has potential applications in numerous neurologic and psychiatric conditions that arise from abnormal control of glutamate."

A large, multi-center clinical trial
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
5-Jan-2005


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