Antibiotic Recipe Keeps Neurons Alive

A common antibiotic partly protects mice from neurodegeneration, new research shows. If the finding translates to humans, the drug might help people with amyotrophic lateral sclerosis (ALS), more commonly known as Lou Gehrig's disease, and possibly other neurological diseases.

People who develop ALS lose control of their muscles and usually die within 1 to 5 years. Previously, researchers have tried to correct two biochemical problems that kill neurons in ALS. A third had yet to be exploited successfully: Motor neurons die when their surfaces are overexposed to the neurotransmitter glutamate. ALS patients suffer from this because their neurons have trouble vacuuming glutamate back inside the cells, where it does no harm. Neuroscientist Jeffrey Rothstein at Johns Hopkins University in Baltimore, Maryland, wondered if his team could coax neurons to make more of this transporter protein, and whether that would protect the nerve cells from dying.

The team started with more than 1000 drugs already on the market. Splashing the compounds into neuronal cultures, the team found that a common class of antibiotics that includes penicillin increased the amount of transporter that healthy cells use to reabsorb glutamate by up to 3 times. Then Rothstein's team injected regular doses of ceftriaxone, which belongs to this drug class and can get past the blood-brain barrier, into 3-month old mice whose ALS-like disease was just beginning to show.

The antibiotic delayed the loss of muscle strength by 2 weeks and kept the mice alive on average 10 days--about 8%--longer than untreated animals. They also found that treated mice preserved about a third more motor neurons than sick mice with no treatment, they report in 6 January Nature. Human trials are expected to begin within the year, but Rothstein cautions that many ALS drugs that work in mice haven't helped people.

Calling the experiment an "intelligent approach," neuroscientist Michael Weiss of the University of Washington, Seattle, says he's impressed that team combed through so many FDA approved drugs and managed to hit on a "viable compound." Neuroscientist Robert Friedlander of Harvard University adds the work is "very exciting" and that if the work holds up in humans, the antibiotic might be combined with other experimental drugs that remedy other neurodegenerative pathologies.

Related sites
Jeffrey Rothstein's lab
The ALS Association

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