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Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig's Disease)

Amyotrophic Lateral Sclerosis (ALS), or Lou Gehrig's disease, is a fatal, neurodegenerative disease that destroys nerve cells underlying movement. As these cells degenerate and die, voluntary movement and muscle control become progressively impaired, ultimately leading to complete paralysis. In most cases, the mind is spared as the body deteriorates.

ALS affects as many as 30,000 Americans, crossing racial, ethnic and socioeconomic boundaries. People who are diagnosed with ALS live an average of two to five years; about 10 percent live 10 years or longer. Though improved medical care is helping to extend life expectancy and new treatments address some of the “motor” symptoms of ALS, there is currently no cure, and nothing that can stop the underlying death of nerve cells.

At the Farber Institute for Neurosciences of Thomas Jefferson University, researchers are applying basic science findings about how nerve cells die in neurodegenerative diseases to find better treatments for ALS.

What causes the most common form of ALS is still a mystery, but a small number of cases can be traced to inherited defects in a gene called SOD1. This discovery has enabled scientists to develop an animal model of ALS: rodents bred to express SOD1 develop patterns of cell death and movement deficits that mimic ALS in humans. As in other diseases, these models have driven a better understanding of disease processes for both the inherited form of ALS and the more common “sporadic” form, and have provided a way to test potential treatments.

The precise mechanisms by which SOD1 mutations (about 90 have been identified) cause ALS are not known, but many studies suggest that the defective genes encode a protein that is somehow toxic to motor neurons. This mutant protein is believed to set off a cascade of changes at the molecular and cellular levels that culminates in nerve cell death. Other neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's, follow a similar pattern, but involve different proteins (e.g., beta amyloid in Alzheimer's), and target different groups of neurons for death (e.g., dopamine neurons in Parkinson's).

These similarities make it probable that advances in any one of these diseases will shed corresponding light on the others. Likewise, treatments approaches may have similar goals, even as they target distinct proteins or brain cell populations.

See also: New Hope for Silencing Genes