Research Roundup updates as of January 2002
Unlocking the mysteries of Guamanian ALS
After 50 years of research, the cause behind a cluster of ALS among the native people of Guam — the Chamorro — remains a mystery. Some research groups have pointed to a toxin from the cycad nut, a staple in the Chamorro diet, but that theory has been largely dismissed. Others have observed that Guamanian ALS tends to run in families, and have proposed a strictly genetic origin.
In two recent studies, Gerard Schellenberg of the University of Washington and Veterans Affairs Medical Center in Seattle presents new data suggesting that a mixture of genetic susceptibility and environmental factors causes the Guamanian ALS cluster. (Also see "Wisconsin Expert.")
Shortly after World War II, scientists discovered that about 140 per 100,000 of the Chamorro people had ALS. This figure is, by some calculations, 50 times higher than the worldwide prevalence of the disease. Guamanian ALS is similar to ALS everywhere else, but is also associated with Parkinson-dementia complex (PDC), a disorder that combines the tremor of Parkinson's disease with the memory loss of Alzheimer's.
In the Jan. 8 issue of Neurology, Schellenberg and his group review surveys of Guamanian ALS from the 1950s to the present, and point out that in the 1980s, its prevalence dropped to about 8 per 100,000. In Schellenberg's own survey, from 1997 to 2000, the prevalence was similar. The shrinking but persistent ALS cluster in the Chamorro people suggests an interplay between genetic risk factors and changing environmental factors, he writes.
And in the November issue of Archives of Neurology, Schellenberg's group provides evidence that a variant of the tau gene might be a genetic risk factor for ALS-PDC among the Chamorros. The tau protein is a structural component within neurons, and has been shown to form abnormal clumps in the brains of people who have Alzheimer's, ALS-PDC and other neurodegenerative disorders.
Study of ALS rat supports glutamate toxicity idea
Jeffrey Rothstein, co-director of the MDA/ALS Center at Johns Hopkins University in Baltimore, announced in January that his group has created a strain of rats with ALS.
The achievement, the second of its kind in as many months (see "Stem Cell Therapy Research Taking Several Paths," December 2001), is expected to speed ALS research by improving on the widely used mouse model of the disease. Like the mice, the rats are bred to carry mutations in the SOD1 gene — which cause familial ALS in people — but they're larger and therefore more amenable to surgical procedures.
Rothstein and his group found that the rats went through the characteristic disease process observed in humans and mice with ALS — a rapid degeneration of motor neurons, followed by paralysis. But they also found evidence for a more controversial process — loss of the glutamate transporter EEAT2.
Normally, EEAT2 mops up the brain chemical glutamate, which can be toxic to neurons. Many people with ALS have reduced levels of EEAT2, which has led to the theory that glutamate toxicity plays an important role in the disease. In the rats, Rothstein found an obvious decline in EAAT2 before disease onset. That result strengthens the argument "that the loss of EAAT2 may contribute to motor neuron degeneration" in ALS, Rothstein writes in the Feb. 5 issue of Proceedings of the National Academy of Sciences.
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Three new trials still open
Three new ALS drug trials (see "Enrollment Open," December 2001) are still accepting enrollees.
The trial of celecoxib (Celebrex), an arthritis drug, is being coordinated at Massachusetts General Hospital in Boston. For information contact
Fran Murphy at (617) 726-9122 or firstname.lastname@example.org.
Participants are being screened for a trial of tamoxifen (Nolvadex), a drug used to treat breast cancer, at the University of Wisconsin in Madison. Contact Kathryn Roelke or Jennifer Parnell at (608) 262-7175, (608) 263-9057, (608) 265-2451, or email@example.com. For details, visit www.neurology.wisc.edu/
A trial of minocycline (Minocin), an antibiotic in the tetracycline family, is open for enrollment at the University of New Mexico in Albuquerque. For more information, contact Martha Meister at (505) 272-3194.
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New CoQ10 trial starts in New York
A six-person pilot study at the Eleanor and Lou Gehrig MDA/ALS Center at Columbia-Presbyterian Medical Center in New York suggested that coenzyme Q10 might have some benefit in slowing in the loss of motor neurons in ALS. (See "First Look Suggests Some Benefit From CoQ10," June 2001.)
A new double-blind study will assess the effectiveness of coQ10 on saving motor units, using a neuroimaging technique.
For information about participation, contact Maura Del Bene at (212) 305-1319 or firstname.lastname@example.org.
MDA devotes more than $5.5 million a year to ALS research and services — more than any other U.S. national voluntary, private-sector health agency.
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