Doctors Debate ALS-Statin Connections

Recently, a report from the World Health Organization (WHO) Collaborating Centre for International Drug Monitoring caused a stir in the amyotrophic lateral sclerosis (ALS) community and the pharmaceutical industry by suggesting that widely prescribed cholesterol-lowering drugs might raise the risk of developing ALS.

The paper, published in June in the journal Drug Safety, is extremely cautious in tone, warning readers that the authors do “not do more than raise the signal for further work and analysis” of a possible connection between ALS or what they’re calling an “ALS-like syndrome” and the use of statin medications, such as atorvastatin (Lipitor), lovastatin (Mevacor), simvastatin (Zocor) and others. The paper’s publication led to a front-page story in the July 3 edition of the Wall Street Journal.

In sorting through Vigibase, a WHO database that keeps track of individual reports of possible adverse reactions to drugs throughout the world, I. Ralph Edwards and colleagues found 43 reports of the development of ALS or an ALS-like disorder in people taking a statin medication. They found 40 of them worth a closer look.

In the Drug Safety paper, Edwards and the other authors say they “need to consider that the association between ALS-like syndrome and statins is a chance finding.” But they also caution that they believe their data collection method is free from any obvious reporting biases and that there is some biological plausibility to the hypothesis that statins may be connected to ALS.

Statins are designed to lower serum cholesterol levels, and they probably also lower the cholesterol content of the membranes that surround muscle and nerve cells. That, some hypothesize, could make these membranes more fragile than they would be otherwise.

Previous findings have shown that a small percentage of statin takers develop muscle breakdown serious enough to warrant stopping the drug, and that muscle diseases too mild to be detected can be “unmasked” by statin use.

Last spring, neurologist Ericka Simpson at the MDA/ALS Center at Methodist Neurological Institute in Houston began a trial to test the effects of atorvastatin (Lipitor) in some 50 people with ALS. (See Lipitor (Atorvastatin) - Phase 2 )

Paradoxically, the rationale for the Houston study is that the anti-inflammatory effects of atorvastatin in the nervous system might have benefit in ALS.

The immune system and the inflammatory reactions it sometimes launches are “sometimes protective, sometimes destructive,” says Stan Appel, director of the Houston MDA/ALS Center. “Since it [atorvastatin] does have some anti-inflammatory effects, it could be protective. We’ve got to figure out what’s going on. If our small pilot study looks meaningful and Lipitor is protective, we ought to do a bigger study. If it looks harmful, we ought to spread the word.”

Meanwhile, Appel says, he advises people with ALS to follow the advice of their cardiologists when deciding whether they should continue taking cholesterol-lowering medications.

He emphasizes that he doesn’t believe doctors should tell people to stop taking these medications, even if they have ALS “if the risk is considerable with regard to cardiovascular disease.” He says he doesn’t consider any of the data produced so far to be significant or meaningful and is waiting for the results of the Houston and other studies.

Last January, MDA awarded a grant to epidemiologist Lorene Nelson at Stanford (Calif.) University to evaluate whether statin medications increase the risk of developing ALS or influence progression in those who already have the disease.


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