Scientists discover gene for Lou Gehrig's disease No therapy exists, but potential is seen


In a lustrous finale to one of the most fervid hunts in biology, scientists have discovered the gene behind Lou Gehrig's disease, a neurodegenerative disorder that results in muscle wasting, paralysis and death.

And, although identifying the gene for an illness is usually just the first step in learning how it works and what happens when it goes awry, in this case the long-sought quarry turns out to be one of the most familiar genes. This familiarity means that potential therapies for the disease may be much closer at hand than had been expected.

In its healthy form, the gene generates an enzyme that deactivates free radicals, those perilous molecular byproducts of normal metabolism that can destroy cells if left untamed.

While researchers warned that defects in this particular gene may account for only a fraction of patients who suffer from Lou Gehrig's disease, also called amyotrophic lateral sclerosis, they held out the possibility that the insights learned from studying the gene might apply to other cases.

Scientists emphasized that although they know a great deal about the anti-radical enzyme, called superoxide dismutase, they still have much to learn about how the enzyme is altered in Lou Gehrig's disease, and how that enzymatic defect might be treated.

The detection of the gene behind Lou Gehrig's disease is of immediate relevance to those in families with a history of the disease.

Only about 10 percent of patients suffer from the hereditary form of the disease, with the rest having sporadic disease, the cause of which is unknown.

But the two types of the disease have apparently identical symptoms and afflict patients at roughly the same age, usually about 50; thus, scientists believe that whatever they learn about the neurodegenerative illness from studying the gene will apply to the treatment of many sporadic cases as well.

For those who come from a family with a history of the disease, researchers can now screen family members to see whether they harbor the defect in the superoxide dismutase gene. This knowledge can help in decisions about whether to bear children or whether to carry on a pregnancy when the fetus has been shown to carry the mutation.

"It's important that people understand that although this is a major breakthrough, at this point we do not have a therapy," said Dr. Robert Horvitz, a researcher at the Massachusetts Institute of Technology who is one of the authors of the report, which appears today in the journal Nature.

Scientists also warned patients about trying to medicate themselves by taking, for example, large doses of Vitamins E and C. These nutrients, like superoxide dismutase, are known for behaving as antioxidants -- mopping up free radicals before they have a chance to do harm.

"We have to be extremely careful," said Dr. Robert H. Brown of the Massachusetts General Hospital in Boston, another author of the paper. "The last thing I would want to see is scores of patients going toxic with extremely high doses of vitamin E."

Nor is there a scrap of evidence, he said, that vitamin supplements will have any impact on the disease.

Still, the discovery of the gene has fanned enthusiasm among those who work with amyotrophic lateral sclerosis. "After 120 years of research, it's probably the most exciting thing that has happened in ALS ever," said Lynn M. Klein, vice president of patient services at the ALS Association in Woodland Hills, Calif.

In seeking the gene, Drs. Brown, Horvitz and Teepu Siddique of Northwestern University Medical School in Chicago led a team of 29 other scientists working at 13 institutions. Their report was accepted for publication in only 36 hours, an extraordinarily brief turnaround time for a scientific journal.

About 30,000 Americans suffer from amyotrophic lateral sclerosis at any given time, and about 5,000 new cases are diagnosed each year. The disease gained its popular name from one of its most celebrated victims, Lou Gehrig of the New York Yankees, who died of the illness in 1941 at the age of 38.

The illness results from the death of the motor neurons, nerve cells that control the muscles. Lacking neurons to power them, the muscles rapidly wither away.

"Usually, an extremity will fail to work, and a person will not be able to button a shirt or tie a shoelace," Dr. Horvitz said. "The problem starts on one side of the body, then it moves to the other side. Muscles degenerate. The person loses weight."

As the neuronal death progresses, patients lose control of their ability to speak, to move, to swallow, even to breathe, although the course varies greatly from patient to patient.

"It's a particularly distressing disease because all mental powers are perfectly preserved," said Dr. Donald H. Harter, senior scientific officer at the Howard Hughes Medical Institute and an adviser to the ALS Society. Patients watch in complete awareness as paralysis overcomes them with astonishing rapidity.

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