ALS Research Roundup September 2007

by Margaret Wahl and Amy Labbe on Sat, 2007-09-01 09:16
Article Highlights:

Reasearch Roundup updates as of August 2007:

ALS-statin interactions probed

A report this summer from the World Health Organization (WHO) Collaborating Centre for International Drug Monitoring caused a stir 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 so-called statin medications, such as atorvastatin (Lipitor), lovastatin (Mevacor), simvastatin (Zocor) and others.

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.

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. (For information, contact Peggy Allred at (713) 441-5191 or

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 or not to continue taking cholesterol-lowering medications.

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.

“As yet, there is no definitive evidence that statin medications increase the risk of developing ALS or make the disease worse,” Nelson says. “Therefore, we cannot recommend that ALS patients on statins discontinue them.

“However, if a person with ALS experiences muscle aches or weakness that appears to worsen in relation to starting a statin medication, the patient and his or her physician should discuss alternative therapies.”

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Supervised resistance exercise slowed functional loss in small study

People with early-stage ALS who engaged in a supervised resistance exercise program had better muscle function after six months than a similar group that participated only in a stretching program, say U.S. and Canadian researchers who recently conducted a 27-person study.

Although the debate persists over whether or not exercise is beneficial or detrimental in ALS, these latest study results represent a potential first step toward resolving the long-standing controversy.

Physical Therapy
Physical therapist Jeanine Schierbecker assesses the strength of a man with ALS.

The research team, which included a physician and physical therapists associated with MDA/ALS Centers in New York and St. Louis, found that, even though exercise may not have any ultimate influence on disease progression, it may temporarily slow loss of strength and function and minimize muscle wasting that results from lack of movement.

In a paper published in the June 5 issue of Neurology, the investigators say they randomly assigned 13 out of 27 subjects with mild to moderate weakness to a regimen of stretching and resistance exercise. They assigned the other 14 to a control group that performed only stretching exercises. Eight people in the stretching-plus-resistance exercise group and 10 in the stretching group completed the trial.

The stretching routine was the same for both groups and was performed daily, while those in the resistance exercise group added individualized exercises using cuff weights three times a week.

After initial instruction, all exercises were performed at home, with telephone monitoring every two weeks and physical assessments every month.

After six months, those in the resistance exercise program had a smaller decline in muscle strength than those performing only stretching exercises.

“Our study, although small, showed that the resistance exercise group had significantly better function, measured by the ALS Functional Rating Scale and upper and lower extremity subscale scores, and quality of life without adverse effects as compared to subjects receiving usual care,” said study author Julaine Florence, a physical therapist at Washington University in St. Louis.

Physical therapist Jeanine Schierbecker, also a study author and  physical therapist at Washington University, said her “best recommendation is that, if a patient with ALS is interested in pursuing an exercise program, they should discuss it with their physician and be evaluated by a knowledgeable, ALS-savvy physical therapist.”

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TGen whole-genome results published

MDA-supported researchers at TGen used microchip technology to compare the genes of people with and without ALS.

Results of a “whole-genome association” study conducted at the Translational Genomics Research Institute (TGen) in Phoenix and initially announced in November were published online Aug. 1 in the prestigious New England Journal of Medicine.

The MDA-supported TGen researchers used state-of-the-art microchip technology to scan the entire genome (set of genes) of approximately 1,200 people with and 1,500 people without sporadic (nonfamilial) ALS. They identified minute DNA differences between the two groups at 50 locations, one of which was statistically significant even after the most stringent mathematical tests were performed.

The MDA-funded ALS Therapy Development Institute will be collaborating with TGen to interpret TGen’s results.

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