Fat abnormalities offer a new clue to Gehrig's disease

WASHINGTON -- Mark Mattson examined the spinal cords of victims of Lou Gehrig's disease and spotted something surprising -- abnormal buildup of fat-like substances in the cells the deadly disease targets.

Could somehow blocking that fatty buildup slow the inexorable paralysis of the disease? The National Institutes of Health neuroscientist is trying to find out, injecting mice genetically destined to get Lou Gehrig's with an experimental drug that appears to block the abnormal lipids.

It's a novel theory, and the drug is years away from being tested in people. But no one knows what causes Lou Gehrig's, and several recent treatment attempts have failed -- so every new clue is welcome, and scientists are awaiting Mattson's results with both hope and caution.

"It really looks like a very interesting thing, but there've been false leads before," says Dr. Daniel Newman of Henry Ford Hospital in Detroit, who treats patients with Lou Gehrig's, formally known as amyotrophic lateral sclerosis or ALS.

Jumping to conclusions

But the theory already is generating speculation among patients about whether diet plays a role in ALS. Researchers recently found links between a high-fat diet and another neurologic disease, Alzheimer's. The NIH does plan to study whether eating certain fatty acids might affect ALS, but skeptical specialists are telling patients not to make drastic dietary changes yet.

"Patients are starting to jump to the conclusion that diet makes a difference. That's leaping to a conclusion," warned Lucie Bruijn, science director of the ALS Association.

Some 30,000 Americans have ALS, which results in a creeping paralysis as movement-controlling neurons, or nerve cells, in the spinal cord and brain are progressively destroyed. It typically strikes in the 50s, and patients often die within five years of the first symptoms, as paralysis leaves them unable to eat or breathe. The only treatment prolongs life about three months.

A small proportion of ALS is inherited, but what causes most cases is a mystery.

Lipids are building blocks of fat, and Mattson, neuroscience chief at NIH's National Institute on Aging, knew that the way people metabolize lipids changes with age. Also, changes in lipids inside cells play a role in cell death. So Mattson's lab examined lipid levels in ALS.

Found fat byproduct

The scientists discovered that the spinal cords of ALS patients harbor significantly higher levels of several lipids than do healthy people's spinal cords. While cholesterol was somewhat elevated inside the cells, of greater concern were lipids called ceramides, the byproduct of a fat important in the normal insulation of nerve cells.

Studying autopsy tissue doesn't reveal when the abnormal fats appeared. So Mattson next studied mice genetically engineered to get ALS -- and found ceramide levels rose before the mice ever showed ALS symptoms, suggesting ceramides play a crucial role in neuron degeneration.

For now, Newman advises patients just to eat the moderate-fat diet the government recommends and take antioxidants such as vitamin E.