Antibiotics Eyed to Treat Nerve Disorders

WEDNESDAY, Jan. 5 (HealthDayNews) -- A group of antibiotics that includes penicillin is showing potential for preventing the nerve damage endemic in Lou Gehrig''s disease, and could help other neurological disorders, a new study finds.

While the effects have so far been seen only in mice, the authors already have funding to start a clinical trial later this year, said study co-author Lucie Bruijn, science director and vice president of the ALS Association. The report appears as a research letter in the Jan. 6 issue of Nature.

ALS is the acronym for amyotrophic lateral sclerosis, popularly known as Lou Gehrig''s disease. It causes progressive weakness and paralysis, and is usually fatal within three to five years of diagnosis.

Although the study looked specifically at ALS, the implications may be carried much further to other disorders that are marked by a loss of nerve function, including dementia, stroke and epilepsy.

The current findings grew out of a larger initiative, sponsored by the National Institute of Neurological Disorders and Stroke, to screen U.S. government-approved compounds to see if they might have any benefit for ALS.

About 20 of 1,040 drugs and compounds the researchers screened showed a high expression of GLTI protein, a key gene involved in Lou Gehrig''s. An analysis this group found that beta-lactam antibiotics, the granddaddies of these drugs, were overrepresented.

Beta-lactam antibiotics, including penicillin and its derivatives as well as cephalosporin, stimulated the expression of GLTI as early as 48 hours after treatment. Beta-lactam antibiotics were first discovered in 1928 with the use of penicillin, and are to this day the most widely used antibiotics, the study reported.

The ability of the drugs to have this effect has nothing to do with their antibiotic properties, study authors stressed. "They are not being used as antibiotics," said Bruijn. "ALS is by no means a bacterial infection."

Instead, the drugs turned on the GLT1 gene. That, in turn, increased the number of transporters available to remove the neurotransmitter glutamate from the nerves. "This is a transporter that is key in removing excess glutamate from the surrounds of the motor neurons," Bruijn explained. "This has therapeutic implications because we know glutamate is a problem. Too much of it has serious consequences, not only in ALS but also in other neurodegenerative diseases."

In mice that had been genetically engineered to have the equivalent of ALS, daily injections of the drug ceftriaxone (Rocephin) stemmed the loss of nerve cells and muscle strength and also extended survival by 10 days.

While penicillin had the best effect on nerve protection in laboratory dishes, Rocephin did the best in mice, probably because it more easily penetrates the blood-brain barrier.

According to the study authors, this is the first time that drugs have been shown to have an effect on glutamate transporters.

The drugs still have a long way to go before their efficacy in humans is proven. "There''s a huge challenge moving from an animal model to a clinical trial," Bruijn said. "I don''t think there''s any way we can know how successful this will be in patients. We''re confident it will be safe and it seems to be a very good way to go, because it''s working on mechanisms we have a lot of faith in."

Bruijn also said that other medications had shown promising results in the initial screening but they need further verification before they are announced.

Johns Hopkins University and study lead author Dr. Jeffrey Rothstein, a professor of neurology at Hopkins, are seeking patents to cover the use of antibiotics to treat neurological conditions.

More information

For more on ALS or Lou Gehrig''s disease, visit the ALS Association.

SOURCES: Lucie Bruijn, Ph.D., science director and vice president, ALS Association; Jan. 6, 2005, Nature