December 21, 2006

Research Update — from ALSA’s National Office

Modifier Genes Sought for ALS Progression in Mice

Roberta Friedman, Ph.D., ALSA Research Department Information Coordinator

[Quick Summary: Additional funding is awarded to continue progress in finding modifying genes in the mouse, which have human counterparts that may change how ALS plays out in people.]

The ALS Association is pleased to award new funding for the successful progress of research that is uncovering possible modifying genes in mice that could affect progression of the disease, amyotrophic lateral sclerosis (also called Lou Gehrig’s Disease).

“These studies are an exciting addition to the growing body of evidence that modifying genes can change the expression of the disease,” said Lucie Bruijn, Ph.D., science director and vice president of The ALS Association. “We are pleased that the ongoing investigations are continuing to show such promise.” Funding for the project was initiated by The ALS Association.

Mice have been engineered to produce mutant copper-zinc superoxide dismutase (SOD1), the protein changed in some inherited cases of the disorder. These mice are created and maintained by breeding to stock strains of mice which differ slightly in their genetic makeup.  Even these small genetic differences can contribute to the way a disease develops: time to onset, time of disability and time to death. This is the case for the mutant mouse with a change of the amino acid in position 93 in the SOD1 protein, the so- called G93A mutant mouse, as shown by Kevin Seburn, Ph.D, and Gregory Cox, Ph.D., collaborating at the Jackson Laboratory in Bar Harbor, Maine.

Cox and Seburn have determined that only a few genes are responsible for the variation in disease onset observed in two separate lines of SOD1 mutant mouse that differ in their genetic background.  They also have in hand a recently identified strain carrying a modifier gene that delays disease onset in another neurological disorder. There is evidence that this gene could also affect the course of ALS in mice, and the requisite breeding studies are underway to see if this is the case.  Results of this work will undoubtedly improve our understanding of the SOD1 disease pathway and will hopefully point toward possible new therapeutic targets.

“It is encouraging that this evolving gene project has come so far and now stands on the threshold of our goal, to find genes that tell us enough about the disease mechanisms to begin to target therapeutics to change its course,” Bruijn said.

See The ALS Association’s web site under the research tab to learn more about ALS Research.  Go to the following links for further information about laboratory models of ALS and the genetics of ALS.