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First international gene screen for typical ALS is on track

30.11.2006
Packard Center researcher, support, helps key study

The largest-scale search for genes that underlie sporadic amyotrophic lateral sclerosis (ALS), the most common form of the disease, has crossed its first hurdle with the successful compiling of genetic information on more than 1,000 patients and controls.

Researchers in the study, supported by The Packard Center for ALS Research at Johns Hopkins, the National Institute of Neurological Disorders and Stroke (NINDS) and the ALS Association, present their initial findings this week at the 17th International Symposium on ALS/MDA at Yokohama, Japan. The symposium is the major venue, worldwide, for reporting studies on the disease.

It’s a good beginning to the first broad screening for genes for the “spontaneous” illness which, like all ALS, destroys the motor neurons that enable movement, including breathing.

... more about:
»patients »sporadic

Packard Center grantee Bryan Traynor and John Hardy, both with the NIH, are leading an American and Italian team of researchers in the million-dollar project. “If all goes well,” Traynor says, “the work will clarify the role of genes-or lack of it-in sporadic ALS. That role has long been uncertain,” he explains. “We don’t know, for example, if sALS is triggered by a handful of interacting genes or genes plus environment or environment alone. Our work aims to clarify that.”

In the study, DNA was collected from patients and healthy controls and successfully scanned for specific patterns that appear more frequently in those with the disease than those without it.

Critical to the work-known to scientists as a high resolution, genome-wide association study-is its technology. It’s a high-throughput approach (that is, it treats many samples simultaneously) that uses robotics and just-available gene finder chips to mine each patient’s DNA for information with a speed and accuracy not possible six months ago.

The project, which began last spring, was completed in record time, reflecting the highly collaborative nature of the involved scientists and clinicians. The NINDS, for example, contributed the American samples in the study from among those that ALS clinicians at multiple medical centers nationwide sent to its new national repository.

The researchers anticipate important analysis and conclusion-drawing will occur in the next few months.

Finding genes that lead directly to ALS or that predispose people to the disease should provide new targets for therapies. In the decade since discovering the cause of some inherited forms of ALS-namely, a mutation producing a flawed version of the enzyme superoxide dismutase (SOD1)-a handful of other ALS-related mutations have been brought to light.

The genetic underpinnings of sporadic ALS, however, are far less certain. Sporadic ALS, affecting 90 percent of ALS patients, apparently arises spontaneously without family history. Even though the disease is clinically indistinguishable from the ALS that runs in families, different genes may be responsible for each. Something is held in common, however, in the way that they both kill motor neurons. That’s why a gene change identified in one type can help understand the other.

Finding a scientifically significant tie between a gene or genes and ALS in this work will set the stage for even larger international investigations. “But even if we get no associations,” says Traynor, “that would suggest that sALS isn’t gene-based, that we should focus instead on the environment.”

Marjorie Centofanti | EurekAlert!
Further information:
http://www.jhmi.edu

Further reports about: patients sporadic

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