MDA RESEARCHERS FIND DIETARY SUPPLEMENT PROMISING IN LOU GEHRIG'S DISEASE

The metabolic supplement, which has previously shown therapeutic benefit in animal models for Huntington's, Parkinson's, other neurologic diseases and Duchenne muscular dystrophy, warrants additional study according to lead researcher and MDA grantee M. Flint Beal of the Cornell University Medical Center in New York City. "Clinical trials are now being planned," said Beal, "as our study of mice with a genetic form of ALS shows creatine to be at least twice as effective as riluzole, the only currently approved drug for people with ALS."

Dr. Leon Charash, chairman of the MDA Medical Advisory Committee, said, "Creatine is well tolerated by man, and harnessing its apparent ability to buffer and stabilize the production and transportation of energy within cells could yield important health benefits for people with ALS and other progressive diseases. MDA is eager to fund the human trials necessary to determine what this elegant animal study may mean to the tens of thousands affected by inherited and sporadic forms of ALS."

Creatine works by an entirely different mechanism than riluzole. The fact that the mechanism is different suggests that the two drugs could be used together to achieve a beneficial, additive effect, researchers say. Riluzole works by blocking a body chemical called glutamate, while creatine works by affecting the energy-producing mechanisms of cells. MDA research has focused on both strategies, as well as others, for the treatment of ALS.

Charash underscored that this research must be done quickly, as "it will be difficult to keep ALS patients off creatine until safe and effective dosage levels can be determined. The findings in mice were dosage dependent and if creatine is found to be beneficial in treating human ALS, the correct dose needs to be determined before patients should take the supplement."

Creatine is a small molecule that can be turned into the high-energy compound phosphocreatine by the body. Because it creates bursts of energy, it is especially popular among athletes. Phosphocreatine is important for the rapid generation of energy in tissues that are very metabolically active such as the brain and muscle.

Beal and colleagues at Massachusetts medical research centers in Boston, Bedford and Cambridge say initial trials will study the effectiveness of creatine in treating ALS in humans. Subsequent trials in both mice and humans will study the effects of combining creatine with riluzole.

ALS is a rapidly progressive disorder that causes degeneration of the neurons that control the voluntary muscles. Affecting some 35,000 Americans, ALS results in total paralysis and death usually within five years from the time of diagnosis.

The current findings reported in the March issue of Nature Medicine show that creatine supplementation in the diet of mice engineered to have an ALS-causing mutation extended their lives by an average of 26 days longer than such mice that didn't get the supplement. The effect of the orally administered creatine was dosage-dependant, with significant improvements in survival achieved with both one- and two-percent creatine in drinking water.

Researchers suspect that creatine is able to increase survival time in mice with ALS because it protects the muscle-controlling nerve cells (motor neurons) normally damaged in the disease. The motor neurons of the ALS mice are depleted by the time the mice are four months old.

However, Beal and colleagues found that four-month-old mice with ALS that had received creatine in their diets had the same number of motor neurons as healthy mice of that age.

Beal suggests that there are two possibilities to explain how creatine may protect neurons against the effects of ALS. The first possibility is that taking creatine increases the energy levels in the brain - levels that may be compromised in ALS by damage to the main powerhouses of the cells, the mitochondria.

"The second possibility," said Beal, "is that creatine may have direct effects on the mitochondria by inhibiting the mechanism by which some types of cell death are triggered. Recent data indicates that mitochondria play a pivotal role in maintaining the health of motor neurons and other cells."

Beal and colleagues are currently doing more studies to try to understand the mechanism by which creatine protects nerve cells.

With an ALS program more than three times larger than the combined programs of all other ALS agencies, MDA leads the worldwide scientific battle to find treatments and cures for ALS. The Association has invested nearly $100 million fighting this relentless disease, and was instrumental in developing the first approved drug that slows the destruction of ALS in some people. MDA's national network of 230 clinics and 17 ALS research and clinical care centers provides an unparalleled range of services to families affected by ALS.

MDA is a voluntary health agency working to defeat 40 neuromuscular diseases through programs of worldwide research, comprehensive services, and far-reaching professional and public health education. The Association's programs are funded almost entirely by individual private contributors. For more information or referrals to MDA clinics, call 1-800-572-1717 or visit www.mdausa.org.