Promising New Drug Fails to Help People With Lou Gehrig's Disease

From the WebMD Archives

Oct. 13, 1999 (Seattle) -- A drug widely expected to help people dying of amyotrophic lateral sclerosis (also known as ALS, or Lou Gehrig's disease) has failed its first major test, researchers reported Wednesday at a scientific meeting.

The researchers had high hopes that gabapentin, a drug used to treat epilepsy, would slow the progress of ALS, a disease that affects more than 25,000 Americans and usually leads to paralysis and death within a few years. But in a study that was the final hurdle before seeking Food and Drug Administration (FDA) approval, gabapentin proved no better than a sugar pill, the researchers reported at the 124th Annual Meeting of the American Neurological Association.

"It was very disappointing. We were crushed," says Robert Miller, MD, who led the team that tested gabapentin. Miller, who is also the chairman of neurology at California Pacific Medical Center in San Francisco, says the failure means that people with ALS still have only one drug proven to slow the disease. And that drug, called riluzole, produces only a modest benefit, he says.

Scientists had been optimistic about gabapentin because it worked in mice with a condition that resembles ALS, and it appeared to help people with ALS in a smaller study, Miller says. Also, like riluzole, gabapentin prevented the accumulation of a substance called glutamate, which is thought to damage the nerves that control muscles.

But in the large study, which took 9 months and included more than 200 people with ALS, the drug failed to slow decreases in muscle strength, the ability to breathe, or the ability to carry out everyday tasks. In every category the researchers measured, people taking the drug were no better off than people who took a placebo.

The study was designed to detect a difference as small as 35% between people taking the drug and those on placebo, Miller says. So it's possible that gabapentin has a very small beneficial effect that went unnoticed.

Miller says that he expects news of the drug's failure will be devastating to ALS patients, especially the thousands who have been taking gabapentin hoping it would slow the disease. He says nearly one in three ALS patients in the U.S. has been taking the drug.

But Miller, who has been involved in more than a half-dozen unsuccessful trials of ALS drugs, says that both patients and researchers have grown accustomed to disappointment. "This is a disease that's not going to give in easily," he says.

Daniel Drachman, MD, an ALS researcher and professor of neurology at Johns Hopkins University in Baltimore, tells WebMD that he remains optimistic about new therapies for the disease. "We know we are on the right track," he says. "But at the moment we still have only one drug."

Miller says that researchers are looking at other approaches to treat ALS, including gene therapy and the use of antioxidants, such as vitamin E, which are thought to protect cells from damaging chemicals produced by the body.

But Miller says the search for a cure for ALS is likely to proceed slowly because scientists still do not understand what triggers the disease.