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Prize4Life and the Jackson Laboratory team up to fight ALS
Date:12/10/2009

Prize4Life, an organization dedicated to finding a cure for amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), is partnering with The Jackson Laboratory to help more researchers identify treatment candidates that increase the lifespan of mice that model ALS.

The Jackson Laboratory will provide the most widely used ALS mouse models, and expert guidance for how to work with them, to researchers participating in the Prize4Life $1 million challenge. Established in 2008, the Avi Kremer ALS Treatment Prize is named for a Harvard Business School student who was diagnosed with ALS and who, with fellow students, founded Prize4Life in 2004 to accelerate research for treating and curing ALS by using large inducement prizes.

In 2006, Prize4Life opened the ALS Biomarker Challenge, offering a $1 million prize to the researcher who could find a biomarker that would reliably measure disease progress in ALS patients. Both prizes are open to all interested researchers and have attracted research teams from industry and academia from around the world.

Teams competing for the Avi Kremer ALS Treatment Prize are pursuing several approaches, including therapies to replace damaged cells, protein-based therapeutics, and small-molecule drugs that interfere with ALS-implicated pathways.

ALS progressively erodes muscle control, including the ability to breathe. Five-year survival is rare. According to Jackson Laboratory ALS researcher Gregory Cox, Ph.D., fewer than 10 percent of the 5,600 new ALS cases diagnosed in the United States each year can be directly attributed to family genetics. "This disorder is so devastating, and our knowledge base is still so incomplete," says Dr. Cox. "Our expectation is that there will be a genetic susceptibility to ALS, that it's not completely random."

The first genetic factors to be conclusively linked to ALS, albeit in only 3 percent of cases, are mutations in the antioxidant enzyme superoxide dismutase-1 (SOD1) gene. Most ALS research today concentrates on the pathogenesis of SOD1 mutations in laboratory mice. The most widely used ALS mouse models, popularly known as SOD1 mice, are distributed from dedicated supply colonies maintained by The Jackson Laboratory's JAX Breeding Services.

The Laboratory currently distributes 12 different SOD1 models -- with different forms of the SOD1 mutation and on different genetic backgrounds. Among the most widely used of these models is JAX Mice strain B6SJL-Tg(SOD1*G93A)1Gur/J (002726). Like several other SOD1 models, this one has a high copy number of the mutant human superoxide dismutase 1 (SOD1) transgene, which contains the Gly93-->Ala (G93A) substitution. The mutation underlies the most studied form of inherited ALS in humans. The mice lose motor neurons in the spinal cord, become paralyzed in one or more limbs, and die by four to five months. These phenotypes closely model those of human ALS (Gurney et al. 1994).

"An effective treatment for ALS is desperately needed, and the existing [SOD1] mouse model is the primary gateway to clinical trials," wrote prominent ALS researcher Tom Maniatis, Ph.D., on CheckOrphan.org. Maniatis is chair of Columbia University's Biochemistry and Molecular Biophysics Program, a member of Prize4Life's scientific advisory board, and a trustee of The Jackson Laboratory.

Many of the initial studies conducted with Tg(SOD1*G93A)1Gur/J mice have provided a wealth of information and insight on how to best use the mice in preclinical trials. However, like other highly expressed transgenes, the G93A transgene can spontaneously lose copy number, which can greatly confound experimental results. Therefore, the mice need to be handled carefully. When Prize4Life approached The Jackson Laboratory to establish a dedicated supply for their researchers, Chief Operating Officer and Chief Scientific Officer Melanie Leitner, Ph.D. and Scientific Program Officer A. Sheila Menzies, Ph.D., together with Jackson Associate Director for Genetic Resource Science Cathleen Lutz, Ph.D., produced a companion set of informational materials titled Working with ALS Mice: Guidelines for Preclinical Testing & Colony Management, which can be downloaded in PDF format at www.jax.org/jaxmice/literature/factsheet/working_with_ALS_mice.pdf.

"Prize4Life spearheaded this effort," says Lutz. "It's really targeted to those investigators who are new to the field of ALS and who are working with the SOD1 mice and designing their preclinical trials. The scientific community has learned a great deal about how to work with these mice over the years. It's important to make that information more widely known so that valuable time and resources aren't wasted by repeating past mistakes.

"If Prize4life succeeds in its goal of bridging the critical steps between academic discovery and therapy in the clinic, it could have major implications for ALS patients and for any group trying to solve a biomedical problem," Lutz adds. Interested researchers can learn more at www.prize4life.org.


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Contact: Joyce Peterson
joyce.peterson@jax.org
207-288-6058
Jackson Laboratory
Source:Eurekalert

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