More than a dozen of penicillin's relatives, known as beta-lactam antibiotics, were among protective agents identified by a National Institutes of Health-funded project to screen 1,040 Food and Drug Administration-approved drugs for new uses. The newfound ability of these antibiotics to activate glutamate transporters and to protect nerves, and the drugs' potential therapeutic use in neurological conditions, are covered by patent applications held by Rothstein and Johns Hopkins and licensed to Ruxton Pharmaceuticals Inc.
Of the antibiotics, penicillin protected nerve cells best in laboratory dishes, but ceftriaxone had the best results in mice, probably because it more easily crosses into the brain from the blood, the researchers report.
Rothstein and his colleagues determined that the antibiotics' benefit stems from their newly recognized effect on glutamate's Jekyll-and-Hyde effects. In the brain, glutamate normally excites nerves so that electrical signals can travel from one to the next. But too much of the chemical can overstimulate and kill nerves, a factor in ALS and some other diseases.
In a series of experiments, the researchers discovered that the antibiotics activate the gene encoding glutamate's main transporter in brain cells. Rats and mice that received daily ceftriaxone for up to a week had triple the usual amount of the transporter, known as GLT1, in their brain cells, an effect that lasted for up to three months after treatment.
"Glutamate is just one of many messengers brain cells use to communicate with one another, and this is just one of the transporters that move glutamate," sa
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
5-Jan-2005