New transgenic rat model of ALS expands research possibilities

A team of scientists led by drug maker Wyeth-Ayerst and Johns Hopkins have engineered and tested a new rat model of Lou Gehrig's disease they say is far easier to work with than earlier mouse models.

Because of their larger size, the rats should expedite evaluation of novel treatments, such as those using stem cells, as well as deepen understanding of the fatal disease also known as amyotrophic lateral sclerosis (ALS), the scientists say. The "transgenic" rat, which carries a human gene, already has revealed the important role played by brain cells called astrocytes, a role obscured in mice.

The ALS rat, believed to be the first transgenic rat model of a neurodegenerative disease, moves from onset of symptoms through to ALS-like disability more quickly than ALS mice, making changes in cells in the rats more striking from day to day, the scientists report in the Jan. 29 online edition of the Proceedings of the National Academy of Sciences.

"The transgenic rats are a powerful tool," says neurologist Jeffrey Rothstein, M.D., director of the Center for ALS Research at Johns Hopkins and an author of the report. "Mice are just too small, for example, for reliable infusions into their spinal cords, the direction research on stem cell treatment is heading."

Scientists at Wyeth-Ayerst engineered the rats to carry an abnormal human gene for superoxide dismutase (SOD1), an enzyme that normally breaks down free radicals, highly reactive molecules that quickly damage DNA and kill cells. Faulty SOD1 behavior, caused by a number of different genetic mutations, is at the root of roughly one-fifth of inherited ALS cases.

The SOD1 rats, like the SOD1 mice before them, develop a disease very similar to ALS in humans, which is characterized by the death of motor nerve cells throughout the central nervous system. The rats are "symptom-free" for a longer time, but then deteriorate much more rapidly than the mice.

While the faster disease

Contact: Joanna Downer
Johns Hopkins Medical Institutions

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