Thalidomide for Lou Gehrig's Disease?

Tests on Mice Show Promise for Treating Amyotrophic Lateral Sclerosis

Medically Reviewed by Louise Chang, MD on March 16, 2006
From the WebMD Archives

March 16, 2006 -- Tests on lab mice show that the drugs thalidomide and lenalidomide may help curb amyotrophic lateral sclerosis (ALS), widely called "Lou Gehrig's disease."

ALS is a progressive degenerative neurological disorder that has no cure. For reasons that aren't understood, the nerve cells of the brain and spinal cord that control voluntary muscle movement gradually deteriorate. As a result, muscles waste away, leading to paralysis and death, usually in two to five years.

ALS is often nicknamed "Lou Gehrig's disease" after the baseball player who died of ALS in 1941.

Thalidomide and lenalidomide showed promise in mice with ALS, the researchers report. However, they stress that they don't know yet if the same would be true for people.

The study appears in The Journal of Neuroscience.

About the Study

The researchers included Mahmoud Kiaei, PhD, of Cornell University's Weill Medical College.

Kiaei and colleagues didn't test the drugs on any people. But they did study samples of spinal cord tissue from 12 deceased people, half of whom had had ALS.

The tissue samples showed high levels of two inflammatory proteins. Those proteins -- called tumor necrosis factor alpha (TNF-alpha) and fibroblast-associated cell-surface ligand (FasL) -- both turned up in high levels in untreated mice with ALS.

The researchers split the mice into three groups. One group of mice got thalidomide, another group got lenalidomide, and the third group got injections of salt water, which has no medicinal use in ALS.

Study's Results

The researchers tested thalidomide and lenalidomide on the mice to see if those drugs would block the inflammatory proteins TNF-alpha and FasL.

The drugs appeared to have that effect. Levels of TNF-alpha and FasL fell in the mice treated with thalidomide and lenalidomide. Survival also improved and ALS worsened more slowly in the drug-treated mice.

However, much work lies ahead to see if the same is true for people.

"Drug metabolism and other factors are just so different between mice and humans," Kiaei says in a Cornell news release. "So far, none of what's worked for ALS in animal models has translated to effective treatments."

"Still, right now we have so little to offer patients in this devastating disease," Kiaei adds. "This does offer new hope."

Next Steps

Kiaei says the next step is "to test and see whether these drugs work in mice if we administer them at the time of disease onset. That's much more relevant for patients because that's when they would first be prescribed medications to fight ALS."

Thalidomide is known to cause severe birth defects. It is currently approved by the FDA -- with strict rules to help prevent birth defects -- to treat debilitating and disfiguring skin sores associated with erythema nodosum leprosum, an inflammatory complication of leprosy.

"Because pregnancy is not an issue for women with ALS, the concern with birth defects should not slow this research or thalidomide's potential use in patients," Kiaei says. "Still, we should always make sure thalidomide is used under strict conditions, should clinical trials begin."

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SOURCES: Kiaei, M. The Journal of Neuroscience, March 1, 2006; vol 26: pp 2467-2473. WebMD Medical Reference: "Understanding ALS -- the Basics." FDA: "Thalidomide Consumer Information." News release, Weill Medical College of Cornell University.
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