Mayo is next step in ALS research
Fri, Dec 1, 2006
E-mail this story
Related Stories• Study gives hope to Lou Gehrig's patients - Fri, Dec 1, 2006
. By Jeff Hansel

The Post-Bulletin

Scientists at the Translational Genomics Institute analyzed the genomes of 3,200 individuals to find the genetic triggers of sporadic amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease.

Next, researchers are preparing a search for drugs to treat the devastating illness. They found 50 genetic anomalies involved in development of the incurable condition.

"These genes produce a sort of molecular glue that attaches motor neurons to muscle," says a TGen statement. "It appears that in ALS the nerve is able to peel off the muscle and, when that happens repeatedly, the nerves die."

Some of the genetic abnormalities have never been linked to ALS before.

To find them, researchers analyzed blood samples from 1,200 people with the condition, and 2,000 without.

"This does not mean we've cured ALS," said Dietrich Stephan, deputy director for discovery research at the Translational Genomics Institute (TGen), the non-profit company responsible for the research. This is a necessary and important step toward a cure."

The study was conducted in TGen's Phoenix facility.

Mayo gets involved

The next phase of research, though, will take place in the Collaborative Research Building on the Mayo Clinic campus in Scottsdale.

"That's exactly where we're going to be doing the bulk of these studies," Stephan said.

Translational Drug Development, or TD2, a partnership between Mayo and TGen, will use animal models to test drugs researchers believe have potential to block the effects of ALS.

Scientists will review the genetic abnormalities to see if molecules (in other words, drugs) can be found that would block negative effects on the human body, said Ron Schenkenberger, senior vice president for research and health-care services at the Muscular Dystrophy Association.

One key, he said, is whether the potential compounds are in drugs that are already on the market -- ones approved for other uses by the Food and Drug Administration.

It is not yet known whether treatments can be quickly developed as a result of the discovery, or will instead take many years -- longer than most currently diagnosed with the illness will survive.

But the MDA, which funded the research with a relatively small amount of money -- totaling $1.3 million, according to an MDA spokesman -- says there's a possibility that potential treatments could be found quickly.

That means a search through thousands of drugs already on the market. Because they've been through the FDA approval process, their side effects and risks are already known. That means if an existing drug is found that blocks the effects of ALS, it could be used almost immediately.

Failing that, developing a new drug could take years.

Hanging in the balance are the lives of 30,000 or more Americans now living with the knowledge that life expectancy after diagnosis with ALS, according to the MDA, ranges from two to four years. But famed scientist Stephen Hawking has survived with ALS for many years, Schenkenberger said.

ALS deteriorates nerve cells in the brain and spinal cord that control voluntary muscles, according to MayoClinic.org. Eventually, people who have ALS lose the ability to move their limbs and the muscles needed to breathe.

Using new "microarray" technology by Affymetrix of Santa Clara, Calif., TGen completed the analysis -- from start to finish -- in just nine months. That, says the MDA, shows the speed of research is ramping up.

"Just a couple of years ago, this experiment would not have been possible because there simply wasn't a technology that enabled scientists to sift through the three billion molecules in the genome to find the genetic abnormalities that cause disease," noted Sean George, vice president of the Academic Business Unit at Affymetrix, in a company statement. The study used the same kind of technology that powers supercomputers, George said.

"The quicker we can identify the anomalies, the quicker we can target those for possible intervention," Schenkenberger said.

How soon?

"The time horizon is, at its best, within the lives of people who are still with us -- at its worst within the next two waves of people who are diagnosed," Stephan said.
http://news.postbulletin.com/newsman.../?a=276472&z=2