On 8 August 2003, Science published new research that marks one step toward a potential therapy for amyotrophic lateral sclerosis (ALS), the devastating neuromuscular condition also known as Lou Gehrig's disease. Because of widespread public interest in this disease and its treatment, we are making the full text of this interesting study available free of charge to all visitors to Science Online.

About the research. ALS wreaks its havoc through the degeneration of motor neurons, which in turn causes limb and respiratory muscles to atrophy. To explore possible therapies for ALS, B. Kaspar and colleagues, the authors of the new Science report, did not study the human disease directly, but used a mouse model of ALS -- specifically, mice with mutations in the gene SOD1, which encodes the antioxidant enzyme superoxide dismutase. SOD1 mutations are known to underlie a small percentage of ALS cases in humans, and SOD1-mutant mice show symptoms strikingly similar to those of human ALS patients.

Building on previous work, Kaspar et al. found that, by injecting a viral vector carrying a neurotrophic factor, insulin growth factor 1 (IGF-1), directly into the limb muscles of SOD1-mutant mice, disease progression in the mice was delayed, and the mice survived significantly longer than untreated mice -- even when the therapy was delivered after the mice had started showing overt ALS-like symptoms. The key to the treatment's effectiveness was the delivery method: the viral vector is capable of "retrograde transport" up the entire length of a nerve cell from the muscle to the nucleus of the motor neurons in the spinal cord. This allows the virus to deliver the growth factor directly to the ALS-affected neuronal cell bodies, and bypass the "blood-brain barrier" that makes conventional delivery of drugs to the central nervous system difficult.

Clearly, the new mouse study is a long way from offering a cure for human ALS; human clinical trials are only now being designed, and results from those trials are likely years away. Nonetheless, the research reported in Science could spur another look at the therapeutic potential of IGF-1, an option that seemed to lack promise in earlier trials.

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