November 13, 2005
New Candidates for ALS Therapeutics Presented at Neuroscience Meeting
Scientists presented several promising leads towards new therapeutic strategies for amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease) at the annual meeting of the Society for Neuroscience in Washington, D.C. New avenues may be opened by these preliminary reports at the same time that a prior candidate proved ineffective in the most widely used pre-clinical model of the disease.
In a poster presentation, a German biotech company offered findings obtained with an existing adjunct to chemotherapies in a mouse model of ALS. Armin Schneider, M.D., at Axaron Bioscience in Heidelberg, Germany, explained that a helper molecule called granulocyte colony stimulating factor (G-CSF) can improve the motor performance of mice that model ALS. The mice express a gene for a mutant protein, copper-zinc superoxide dismutase (SOD1), linked to some inherited forms of ALS. They were aided by treatment with G-CSF, a stimulator of the immune system that doctors use to maintain levels of white blood cells, during cancer treatments. The mice survived longer with the G-CSF treatment as researchers at the company showed. Similar findings in stroke and Parkinson’s models are leading the company to investigate the protective potential of G-CSF in several neurological disorders, beyond its proven effects in cancer.
Researchers with Sanofi-Aventis in France reported that a drug similar to the benzodiazepines used for anxiety and sleep difficulties, but acting only outside the brain, appears to help in an animal model of ALS. As presented in a poster by Badia Ferzaz, Ph.D., the drug improved motor ability in the SOD1 mutant mice and prolonged survival although the effect on survival did not reach statistical significance.
Copaxone, a treatment for multiple sclerosis that had shown some potential in ALS, is not effective in a mouse model of the latter disorder, according to results presented by Natalie Perez, working with Jeffrey Rothstein, M.D., Ph.D., at Johns Hopkins University, Baltimore, MD. The drug, also called glatiramer acetate, was tested in SOD1 mutant mice. Various doses and injection intervals were tested but produced no effect on survival of the mice. Disease onset also did not change with copaxone treatment.
Scientists at Wyeth Research in Princeton, N.J. showed in a poster presentation that neutralizing a molecule that slows muscle growth produced significant increases in body weight, muscle mass, and grip strength in transgenic mice and rats that express mutant SOD1, as compared to sham treated animals during early stages of their disease. Inhibiting the regulator, called myostatin, slowed atrophy of the skeletal muscle and also lowered the loss of motor neurons in the spinal cord. No effect on overall survival resulted; however, a significant inhibition of diaphragm muscle wasting appeared at the end of the rodents’ lives. Together these findings suggest that the treatment, which consisted of antibodies that neutralized myostatin, may help the quality of life of patients with ALS.
