Genome-Wide Search Hits Pay Dirt

by ALSN Staff on Mon, 2007-01-01 09:16

On Nov. 30, scientists from the Translational Genomics Research Institute (TGen) in Phoenix announced results of their high-tech scan of all the genes (the entire genome) of 1,200 people with and 2,000 people without ALS. The massive project, supported by a $652,000 grant from MDA's Augie's Quest, a fast-track ALS research program, in collaboration with TGen, is expected to open up a previously unexplored area of ALS research.

TGen Lab
Alana Lysholm-Bernacchi and Sarah Brautigam work at TGen's gene chip fluidics station.

Among the differences that the researchers identified between ALS patients and healthy people were some in genes that influence how nerve fibers interact with muscle fibers, a process that until now hasn't received much attention as a contributor to ALS.

"Our findings indicate these genes produce a sort of molecular glue that attaches motor neurons [muscle-controlling nerve cells] to muscle," said Dietrich Stephan, TGen's director of neurogenomics and the study's principal investigator. "It appears that in ALS the nerve is able to peel off the muscle and, when that happens repeatedly, the nerves die."

Nerve fibers interact with muscle fibers at specific points known as neuromuscular junctions. Normally, a tiny space separates these fibers, across which the chemical acetylcholine has to flow for nerve signals to reach muscle tissue. The molecular glue, or "adhesion molecules," are in the space and keep the nerve and muscle fibers properly aligned. In ALS, the space apparently widens because of a failure of the adhesion compounds to carry out their usual roles.

The fast-track research funding approach used by MDA and a new microarray technology provided by Affymetrix, a multinational company with U.S. offices in Santa Clara, Calif., allowed researchers to quickly scan people's genomes and complete this part of the study in nine months.

Next steps center around high-throughput screening for drugs that act on the biochemical pathways identified by the genome screen.

Normal junction ALS junction

TGen’s results suggest the molecular glue that keeps nerve and muscle fibers properly aligned at the neuromuscular junction may be affected in ALS.

ALSN Staff
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