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Nerve cells of ALS patients harbor virus

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4:20pm, June 7, 2002
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Fragments of viral genetic material show up with unusual frequency in patients with amyotrophic lateral sclerosis, or ALS, but rarely in other people, a new study shows. The report, in the January Neurology, provides the strongest evidence yet that a virus may have a hand in killing nerve cells in this lethal disease.

Although a small percentage of cases is attributable to an inherited mutation, the cause of most ALS is unknown. The illness first attacks the nerve cells in the spinal cord that carry messages to muscles in the legs and arms. It shuts down the signals in these motor neurons, causing the muscles to wither. ALS, also known as Lou Gehrig's disease, typically results in respiratory failure. Death usually occurs 2 to 5 years after symptoms begin.

A group led by researchers at Claude Bernard University in Lyon, France, has found RNA strands of a so-called echovirus in 15 of 17 spinal cord tissue samples from people who died from nonhereditary ALS. The viral particles showed up in spinal tissue from only 1 of 29 people who died of other neurological diseases.

Echoviruses belong to the enterovirus family. This group includes the polio virus, which also kills motor neurons. Researchers have linked echoviruses to meningitis, another central nervous system affliction, but no previous study concluded that these viruses are highly prevalent in patients with ALS.

The disease damages neurons so badly that they are hard to identify in postmortem tissue.

Judging from their size and shape, the cells containing fragments of echovirus RNA in the new study were clearly neurons, says study coauthor Martina M. Berger, a microbiologist currently at the University of California, Irvine. She adds, however, that it's impossible to be certain the cells were motor neurons.

Berger and her colleagues detected the viral particles in the tissue by using a chain reaction that copies small portions of viral RNA millions of times.

Still unresolved is the question of whether echoviruses contribute to the disease or whether ALS simply makes motor neurons susceptible to invasion by the viruses, says study coauthor Bruno Lina, a virologist at Claude Bernard University. Berger suspects that the echoviruses are part of the ALS puzzle and combine with some other factor—perhaps another virus or a genetic defect—to become lethal.

"The study is interesting and provocative . . . but leaves many, many questions unanswered," says Marinos C. Dalakas, a neurologist at the National Institute of Neurological Disorders and Stroke in Bethesda, Md. For example, ALS-damaged nerve tissue shows little inflammation, he says, unlike tissue infected with enteroviruses such as polio.

"Any leads into ALS are always very interesting and exciting because so little is known about it," says Teepu Siddique, a neurologist at Northwestern University Medical School in Chicago. He looks forward to seeing whether other researchers can reproduce the new finding.

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