ALSA Renews Funding for Distribution of SOD1/G93A Rat for ALS Research

Rat Model Producing Progress Toward New Therapeutics

January 14, 2005

The Amyotrophic Lateral Sclerosis Association (ALSA) announces renewed funding to support distribution of a rat model of the disease. With the award, Taconic Labs can continue to provide the mutant SOD1 rat to researchers at reduced cost.

Progress toward new therapeutics for ALS is evident now that researchers have a transgenic rat bearing mutation in the protein, SOD1. The rat model reproduces many features of the human disease.

ALSA facilitated introduction of the rat model for ALS, with the intent to have it available to the research community. Dr. David Howland, principal investigator at Wyeth Research, generated transgenic rats expressing a mutation of G93A in SOD1, and researchers in the Rothstein group at Johns Hopkins, and the Cleveland  group at the University of California, San Diego collaborated with Wyeth to characterize this rat model.

“ALSA initiated funding for Taconic to allow distribution of the rat model to researchers worldwide. Key projects are making headway toward new therapeutics using the model, emphasizing the value of the rat for the community,” commented ALSA Science Director, Lucie Bruijn, Ph.D.

Currently more than twenty laboratories worldwide have ordered the rat, and more than 275 of the animals have been distributed.

A rat model allows for easier manipulation for certain experiments. More cerebrospinal fluid can be obtained from a rat than from the much smaller mouse. In surgeries to test gene and stem cell therapies, the rat spinal cord is easier to access with injections. Continuous infusion of trophic factors directly into the brain by a mini pump is feasible for a rat. 

Investigators using the model include ALSA-funded investigators Clive Svendsen, Ph.D., professor at the Waisman  Center at the University of Wisconsin in Madison and Ole Isaccson, M.D., of Harvard and the Massachusetts General Hospital in Boston.  The researchers are pursuing stem cell strategies for ALS by testing the approach in the rat.  Peter Carmeliet and his colleagues at the Flanders Interuniversity in Belgium have used the rat to demonstrate a role for the trophic factor, vascular endothelial growth factor (VEGF), in ALS.

Don Cleveland Ph.D., professor at the Ludwig Institute of the University of California, San Diego (UCSD) and his colleagues are continuing to investigate whether antisense approaches will help patients with ALS. Antisense prevents specific genes from making protein and can precisely target a defective gene. Findings in rodent models, including the rat, have produced antisense candidates for the disease. 

For further information about the rat, contact researchgrants@alsa-national.org.

To obtain the mutant SOD1 rat, contact Holly Voorhees at Taconic

Links to projects using the rat model:

Howland et. al. Focal Loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotropic lateral sclerosis (ALS). 1604-1609, PNAS - Feb. 5, 2002, Vol. 99, #3.

Dunlop J, McIlvain H.B., She Y, Howland D.  Impaired Spinal Cord Glutamate Transport Capacity and Reduced Sensitivity to Riluzole in a Transgenic Superoxide Dismutase Mutant Rat Model of Amyotrophic Lateral Sclerosis       The Journal Of Neuroscience, March 1, 2003 - 23(5):1688-1696

Storkebaum, E., Lambrechts, D., Dewerchin, M., Moreno-Murciano, M., Appelmans, S., Oh, H., Van Damme, P., Rutten, B., Man, W.Y., De Mol, M., Wyns, S., Manka, D., Vermeulen, K., Van Den Bosch, L., Mertens, N., Schmitz, C., Robberecht, W., Conway, E.M., Collen, D., Moons, L., and Carmeliet, P. (2004) Treatment of Motoneuron Degeneration by Intracerebroventricular Delivery of VEGF in a Rat Model of ALS. Nature Neuroscience. 8: 85-92.

ALSA-Funded Research Presented at Society for Neuroscience Annual Meeting

Can Transplanted Stem Cells Restore Function and Increase Survival?

Direct Brain Delivery of Trophic Factor Prolongs Survival in Rat Model of ALS