Microbe Killer Could Help Parkinson's
Antibiotic may damp inflammation of disease, prevent brain damage
MONDAY, Nov. 26, 2001 (HealthDayNews) -- An experiment showing that a widely used antibiotic can prevent the brain damage caused by Parkinson's disease could open the way to new drug treatments for the neurological disorder, researchers say.
The protective effect has nothing to do with the antibiotic's microbe-killing ability, says Dr. Steven M. Paul, vice president of Lilly Research Laboratories and lead author of a paper in the Proceedings of the National Academy of Sciences. The research was prompted by a number of studies showing that the antibiotic minocycline, a member of the tetracycline family, can prevent inflammation that damages nerve cells in the brain.
Parkinson's disease is caused by the degeneration of nerve cells in a part deep in the brain called the substantia nigra. The disease's effects include rigidity, trembling, difficulty walking and other muscle problems. It affects about 1 million Americans, most of them over the age of 50, and 50,000 new cases are expected this year.
"Minocycline has been shown in a variety of non-brain models to have an anti-inflammatory effect," Paul says. "It was also shown to reduce the damage done by stroke in mice. Given the emerging knowledge that inflammation is important in Parkinson's disease, we studied its effects in an animal model of Parkinsonism."
That model uses mice that are given MPTP, a toxic substance that causes the brain changes associated with Parkinson's disease, such as the death of specific kinds of nerve cells and reduced levels of dopamine, an essential molecule for nerve cell activity.
The experiment was designed to determine exactly how minocycline protects nerve cells. Paul says. The research shows that the antibiotic has two separate protective effects, he says.
First, minocycline prevented damage done by inflammation of glial cells, which make up the majority of brain tissue and provide the support necessary for brain cells to function properly. That effect was more or less expected, given the previous studies, Paul says.
The unexpected effect was that it protected nerve cells against nitrogen oxide, a potentially damaging molecule that is produced by the glial cells. Too much nitrogen oxide in the brain has been linked to the nerve cell damage seen in Parkinson's patients, Paul notes.
Minocycline acts in two ways to prevent that damage, he says. It reduces nitrogen oxide production by glial cells and also blocks the toxic effects of nitrogen oxide against nerve cells.
Minocycline itself is not a feasible treatment for Parkinson's, Paul says. Very large doses are needed to achieve any effect, because relatively little of the antibiotic actually reaches the brain. "But we think it might be a lead [as] to how we can develop drugs for Parkinson's disease," he says. "The cellular mechanisms we have identified could be the route for development of treatment strategies.
"We are continuing our basic research to see exactly how minocycline protects cells. Once we find out, we will be able to screen for other drugs that have the same effect."
One interesting aspect of the study was the fact that minocycline not only prevented nerve damage but also restored some nerve function in the first hours after it was given, says Dr. Stanley Fahn. He is a professor of neurology at Columbia University and scientific director of the Parkinson Disease Foundation. "It is an interesting compound."
But Fahn adds a caution: "A lot of other drugs have been effective in this mouse model, and none of them has been successfully translated to medical use."
What To Do
"We're not advocating that people run out and use minocycline for Parkinson's disease," Paul says. "First, it doesn't get into the brain very well. Second, we wouldn't want to use something that would promote microbial resistance to antibiotics."