Researchers from the University of California, San Diego (UCSD) School of Medicine, led by Pr. Don Cleveland have found a way to slow the progression of amyotrophic lateral sclerosis (ALS) in mice, offering hope to those with ALS or Lou Gehrig's disease. ALS is a progressive disease that slowly attacks the body's motor neurons. Degeneration of the motor neurons in ALS leads to progressive loss of muscle control, paralysis and untimely death. Typically, ALS patients live only one to five years after initial diagnosis. Currently, no one cause has been singled out for the most common form of the disease. Even though researchers have found genes for a variety of inherited types, including the mutated SOD1 gene in the most common familial ALS, exactly how they cause or advance the disease isn't clear. Accumulating evidence shows that cells other than motor neurons play an active role in their ultimate decline and death. In findings published in Science in June 2006, Pr. Cleveland and his colleagues showed that in early stages of inherited ALS, microglia are damaged by mutations in the SOD1 protein, and that these cells then act to significantly accelerate the degeneration of the motor neurons. The present study demonstrates a similar process with astrocytes, key components in balancing the neurotransmitter signals that neurons use to communicate. It is speculated that the non-neuronal cells play a vital role in nourishing the motor neurons and in scavenging toxins from the cellular environment. As with microglia, the helper role of astrocytes is altered due to mutations in the SOD1 protein. Specifically targeting the mutated SOD1 gene in astrocytes did not slow disease onset or early disease, but late disease progression was sharply delayed. Overall, the mice survived an average of 60 days longer, nearly doubling the life expectancy of ALS mice. Silencing SOD1 in astrocytes not only helps protect the motor neuron, but delays activation of mutant microglia that act to accelerate the progression of ALS. These promising findings show that mutant astrocytes are likely to be viable targets to slow disease progression and extend the life of patients with ALS. The study appears in the online publication on Nature Neuroscience's web site.

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