Antibiotic May Help in Lou Gehrig's Disease

TUCSON, Ariz., May 2, 2002 — The antibiotic minocycline looks promising as a potential treatment for the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), the Muscular Dystrophy Association (MDA) announced today.

Minocycline is already being tested in a small, National Institutes of Health-sponsored clinical trial through the MDA/ALS Center at the University of New Mexico in Albuquerque, under direction of neurologist Paul Gordon.

Evidence in support of this pilot trial came from MDA-funded experiments with a related chemical, and from mice with Huntington's disease that benefited from minocycline.

"We already had evidence that minocycline might be effective for ALS," said Sharon Hesterlee, MDA's director of Research Development. "Today's findings provide more direct support for the use of minocycline in ALS."

Robert Friedlander, associate professor of neurosurgery at Brigham and Women's Hospital and Harvard Medical School in Boston, and Serge Przedborski, associate professor of neurology and pathology at Columbia University's College of Physicians and Surgeons in New York, were part of a team that uncovered the most likely mechanism by which the drug works in neurodegenerative disease. The findings appear in today's issue of the journal Nature.

Friedlander and Przedborski have both received MDA support for their work on a phenomenon called programmed cell death, also known as apoptosis. This cell "suicide" program, though normal in other circumstances such as aging, may be excessively active in disorders like ALS.

The researchers believe minocycline blocks a key feature of this type of cell death — the release of a protein called cytochrome c from the cell's energy-producing units, the mitochondria.

The release of cytochrome c is a signal for the cell death program to go into full swing. Blocking this release appears to have kept more cells alive.

In the experiments reported today, the ALS-affected mice that were injected with minocycline retained their movement-related functions longer and lived longer than those treated with a saline solution.

Minocycline (brand names Minocin, Dynacin) is now on the market to treat infections, especially those of the respiratory and genitourinary tracts, and has good penetration into the nervous system. Its action in degenerative disorders is thought to be separate from its infection-fighting mechanisms.

"This study accomplishes two main things," Friedlander said. "First, it confirms the efficacy in a mouse model of a compound that's approved by the Food and Drug Administration, providing further support for evaluating minocycline in a human trial.

"Second, understanding how minocycline works will assist in the development of even more effective compounds for ALS."

Przedborski is also enthusiastic about minocycline.

"For many years now, I have used minocycline for various infectious conditions in my patients," he said. "I never expected that one day I would also consider using this drug to slow neurodegeneration — and that through a mechanism that appears independent from its antibacterial properties."

ALS affects both sexes, usually beginning in middle age, and destroys muscle-controlling nerve cells in the brain and spinal cord. The loss of nerve cells leads to progressive paralysis and usually to death three to five years after onset. No cure exists.

MDA is a voluntary health agency working to defeat more than 40 neuromuscular diseases. The Association has been vitally active in ALS research and services for more than 50 years, and has invested more than $135 million in its ALS program to date. It supports 25 MDA/ALS research and clinical centers across the country.