TGen may have found Lou Gehrig's trigger

Ken Alltucker
The Arizona Republic
Nov. 30, 2006 06:19 AM
Victoria Zismann of Gilbert, a senior research associate, turns off certain gene chip fluidics stations during an experiment Wednesday at TGen headquarters in Phoenix.


Researchers at TGen believe they have narrowed the genetic riddle of Lou Gehrig's disease to 50 abnormal genes, the most common of which have never been identified by researchers before.

The Phoenix-based Translational Genomics Research Institute says the new findings from a computer scan of the human genome leave researchers a trail of bread crumbs as they piece together clues about the mysterious disease, a brain disorder that afflicts up to 30,000 Americans and typically leads to paralysis and death within three to five years.

Although researchers acknowledge much work remains, they believe they have identified differences in genes that play a critical role in the neurological disease.


A healthy person has genes with a molecular stickiness that attach motor neurons to muscle. In the case of patients with amyotrophic lateral sclerosis, or ALS, research shows the nerve can repeatedly slip off the muscle and die, said Dietrich Stephan, TGen's director of neurogenomics and the study's principal investigator.

TGen's findings come from comparing DNA samples collected from more than 1,200 people with the disease to 2,000 healthy individuals.

"This will give us an opportunity to target these molecules to see if there are any drugs that interact with them in any way," said Ron Schenkenberger, the Muscular Dystrophy Association's executive vice president for research and health care services.

Stephan said TGen and other partners are plotting the next step. Money raised to fund the genetic scan has been spent, so TGen will need to raise more money to screen drugs on the biochemical pathways identified by the gene screen.


Man on a mission
Just as important as the findings, Schenkenberger added, is the speed at which researchers finished the study.

TGen and a team of more than one dozen research institutions finished the study within nine months of securing a $652,000 grant through an MDA program called Augie's Quest.

It is named after California fitness entrepreneur Augie Nieto, who was diagnosed with ALS in March 2005.

"He's made this disease his personal mission," Stephan said. He pitched the research project and matching it with TGen's genetic scanning know-how during a trip the LifeFitness Inc. founder made to TGen's downtown Phoenix campus.

"We were funded very quickly. Nine months later, we're done and presenting in Japan," Stephan said. "This was an incredibly focused, high-energy project."

The project was completed at such a quick pace in part because of the powerful computers used by TGen researchers.


Individual genetic map
The technology, known as the 500k microarray, comes from Santa Clara, Calif.-based Affymetrix. The equipment identifies genetic differences between disease-stricken and healthy patients by rapidly producing a genetic map of each individual.

"The surprising thing is the speed with which these abnormalities have been identified," Schenkenberger said. "This results from technology that was not available just a few years ago."

The findings were to be unveiled today at an ALS conference in Japan.

Several research projects contributed to the study. Donated blood came from several MDA/ALS centers, including Houston's Methodist Neurological Institute, San Francisco's California Pacific Medical Center, University of Pittsburgh, New York's Columbia University and a dozen other sites across the nation.

Schenkenberger said the MDA will consider funding another round of ALS research.

"It depends on what the needs are and what the collaboration is," he said. "We're prepared to consider virtually whatever might be required."

Schenkenberger said fitness entrepreneur Nieto is optimistic that $16 million to $19 million can be raised over the next three years to fund fast-track research such as the scan completed by TGen. His life may depend on it.



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