June 7, 2007

The ALS Association Renews Funding for
Distribution of SOD1/G93A Rat for ALS Research

The ALS Association is continuing to provide supplemental funds to support distribution of a rat model of the disease. With the award, the supplier of the rat, Taconic Farms, Inc. can provide the mutant rat to researchers at reduced cost.

The rat model reproduces many features of the human disease that is due to a gene change in producing the protein, copper-zinc superoxide dismutase (SOD1). Investigators world wide continue to use the rat to study the biology and potential treatment of ALS (amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease).

The ALS Association facilitated introduction of the rat model with the intent to have it available to the research community. Researchers at Wyeth, a pharmaceutical company, generated transgenic rats expressing a mutation of the amino acid in position 93 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 http://www.alsa.org/news/article.cfm?id=291. 

“There has been a continued interest in the model and a significant growth; hence we will be committing more dollars to this initiative,” commented The Association’s Science Director and Vice President, Lucie Bruijn, Ph.D.

Laboratories worldwide have ordered the rat, and several hundred 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, a class of proteins that help keep cells healthy, directly into the brain by a mini pump, is feasible for a rat.

Don Cleveland Ph.D., professor at the Ludwig Institute of the University of California, San Diego, 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. Clive Svendsen, Ph.D., at the University of Wisconsin, Madison, also uses the rat in studies aimed at a gene therapy delivery of helpful growth factors for neurons dying in the disease.

For further information about the rat, contact [email protected].
To obtain the mutant SOD1 rat, call (1-888-Taconic) or visit http://www.taconic.com/wmspage.cfm?parm1=1256.

Links to how the rat model was developed:

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 

Links to examples of projects using the rat model:

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. 
http://www.alsa.org/news/article.cfm?id=571

Svendsen collaboration
http://www.alsa.org/news/article.cfm?id=630

Cleveland collaboration
http://www.alsa.org/news/article.cfm?id=912