THURSDAY, Nov. 1 (HealthDay News) -- A trial of the antibiotic minocycline against amyotrophic lateral sclerosis -- Lou Gehrig's disease -- has been halted because patients taking the drug had a significantly accelerated decline in neurological function.
The finding calls into question plans to try minocycline against other neurodegenerative diseases such as multiple sclerosis, said a report published online Nov. 1 in Lancet Neurology.
The study was led by the U.S. Western ALS Study Group.
"There were early indications in animal trials that it [minocycline] might be beneficial," said Robert P. Bowser, director of the University of Pittsburgh ALS research center.
But in a randomized trial that included 412 people with ALS, nerve function in those treated with minocycline deteriorated at a 25 percent faster rate than in those taking a placebo, the researchers reported.
The reason for the accelerated damage isn't known, Bowser said. "Part of the story is trying to figure out the pathway by which the drug is having the effect," he said.
ALS is a disease that attacks motor nerves and causes degeneration throughout the brain and spinal cord. The only known cause of ALS is a mutation of a gene designated SOD1, which is to blame for a limited number of cases. The Yankee first baseman Lou Gehrig is the best-known victim of ALS, but it has also cut short the lives of other athletes, such as pitcher Jim "Catfish" Hunter, as well as former New York Sen. Jacob Javits and the actor David Niven. About 30,000 Americans have the disease at any given time, according to the ALS Association.
Only one drug, Riluzole, has been approved by the U.S. Food and Drug Administration for treatment of ALS. It provides a slight improvement in survival time. "Several drugs are currently in trial, and some look interesting and promising," Bowser said. "But it is too early to tell whether they will be successful."
The problem with minocycline -- which is used to treat acne and urinary tract infections -- and ALS is related to undue extrapolation from animal studies to the human disease, said Dr. Michael Swash, professor emeritus of neurology at Royal London Hospital in England, who wrote an accompanying editorial in the journal.
"The animal model has the human gene in it but lots of copies," he said. "It is not really the same as the human disease."
Animal trials are also untrustworthy because of the size and time of dosages, Swash said. "When the drug is given to mice or rats, the doses are not the same as those given to humans," he said. "Treatment usually starts before the disease commences, so humans get treated a lot later. And human spontaneous ALS does not have the SOD1 mutation, so it is fundamentally different from the animal model."
Effective human trials of treatment for diseases such as ALS should include "a very small number of people, with very good measurements in restricted areas," Swash said. "You need results rapidly to see whether the treatment can be helpful or not. You must find endpoints that are really significant."
Swash said there could be one possible beneficial aspect of the minocycline trial. "Maybe some other drugs we tried that didn't show benefits would show a benefit if used early enough in the disease," he said.
Learn more about ALS from the ALS Association.
SOURCES: Robert P. Bowser, Ph.D., director, University of Pittsburgh ALS research center; Michael Swash, M.D., professor emeritus, neurology, Royal London Hospital, England; Nov. 1, 2007, Lancet Neurology, online