Genetic clues to ALS
BY JAMIE TALAN
jamie.talan@newsday.com

February 20, 2007, 8:40 PM EST

Scientists conducting an entire sweep of the human genome in patients with Lou Gehrig's disease, officially known as amyotrophic lateral sclerosis, have identified 34 possible genetic players -- although no home runs yet, according to a study in the latest issue of Lancet Neurology.

Dr. Bryan J. Traynor, a federal scientist at the National Institute of Mental Health who also works at The Johns Hopkins University School of Medicine, and his colleagues have long been interested in finding out whether there is a genetic trigger in patients with no obvious family history of the fatal motor neuron disease that claimed the famous baseball player.





Like other neurodegenerative diseases such as Alzheimer's and Parkinson's, scientists have identified a small percentage of families who pass along a disease gene. In ALS, that accounts for less than 10 percent of all patients. But Traynor and others believe that genetic abnormalities do play a role in many patients without a family history.

In an attempt to identify genes in these "sporadic" ALS patients, federal scientists at several laboratories at the National Institutes of Health and at Hopkins, in addition to the ALS Association, scanned the entire genome of 276 patients with sporadic ALS and an equal number of people with no history of neurological disease.

The latest genetic technology allows scientists to study more than 550,000 single nucleotide polymorphisms, or SNPs, genetic variations at specific points along the entire geonome. The current estimate is that the human genome comprises about 20,000 genes. In this study, they found a good, strong signal in 34 SNPs.

"This is very exciting," said Lucie Bruijn, science director and vice president of the ALS Association. "Now, scientists have to evaluate these potential genetic candidates. Some could be key players in sporadic forms of the disease."

Bruijn, whose foundation helped design and implement the study, said there is a growing repository of DNA samples from ALS patients, which can be used to study what genes are involved. Once specific genes are targeted, scientists can better understand the disease process and point the way to novel treatments.

There are no treatments that work to stop the damage of motor neurons in the disease. Patients with ALS lose their ability to move as the damage spreads and the cells lose connection to the muscles throughout the body. Patients become trapped inside their bodies, paralyzed, and, on average, die within five years.

"There is no big gene that explains this risk in sporadic patients," said John Hardy of the National Institute on Aging, who collaborated in the project. He suspects that there are many genes that can put people at risk for ALS. Just which genes they are is still not known, but this study moves scientists closer to these genetic targets.

Traynor explained that many of the genetic variants identified are involved in building the structure of the motor neurons, which have very long tails, or axons, that must extend a great length to communicate with muscles throughout the body.
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