Drugs tested for Lou Gehrig’s disease

From San Diego, at the Society for Neuroscience meeting

Two drugs better known for treating other diseases may also help people afflicted with amyotrophic lateral sclerosis (ALS), the fatal neuromuscular illness also called Lou Gehrig’s disease.

One of the drugs is tamoxifen, which is often prescribed to women with breast cancer. Benjamin Brooks of the University of WisconsinMadison and his colleagues became curious about the drug when they noticed that a patient with ALS, who was also receiving tamoxifen for breast cancer, maintained her muscle strength over a period of 4 years.

“Her course of ALS was much less severe than we had expected,” says Brooks.

He then learned of a study showing that tamoxifen protects nerve cells from a chemical called glutamate, which can overstimulate the cells to the point of killing them. Since glutamate overstimulation of muscle-controlling nerve cells occurs in ALS, Brooks decided to test tamoxifen on mice. He and his colleagues infected the animals with a virus that causes ALS-like symptoms; the rodents typically would develop movement problems about 28 days after infection and then die about a week later.

Tamoxifen treatment delayed the onset of symptoms by 8 days and prolonged the animals’ survival by 2 weeks, says Brooks. The investigators have just started a trial of the drug in ALS patients to see if it preserves their muscle strength.

The second potential ALS treatment is celecoxib, the arthritis drug marketed under the name Celebrex. This compound targets an enzyme called COX-2 that drives inflammation in the body. There’s evidence that inflammation plays a role in the nerve cell death seen in ALS, so Jeffrey Rothstein of Johns Hopkins University in Baltimore and his colleagues tested celecoxib on mice genetically engineered to develop a form of the disease.

“Treatment with the COX-2 inhibitor increased survival by up to 4 weeks,” says Rothstein. Riluzole, the only drug approved for ALS patients by the Food and Drug Administration, extends the lifespan of such mice by only 2 weeks, he notes.

Encouraged by the animal results, Rothstein and his colleagues have launched a trial of celecoxib in about 350 ALS patients.