Amyotrophic Lateral Sclerosis


High-throughput drug screening for ALS treatment. The ability to prevent motor neuron death in the presence of ALS-type stress (such as glutamate or mutated superoxide dismutase gene) may identify a useful drug for ALS patients. After treatment, the motor neurons are exposed to stains that make healthy cells appear blue, and dead or dying cells brown. Drug effectiveness is determined by the ratio of live to dead cells.

Motor neuron diseases are debilitating disorders that cause the loss of nerve cells in the brainstem and spinal cord that control movement. Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, accounts for 80 percent of motor neuron disease and occurs in 3-5 people per 100,000. This disease usually strikes people in midlife and is relentlessly progressive, typically resulting in death within five years of the first sign of symptoms. Patients lose the ability to control their limbs, facial muscles, swallowing, and eventually, the ability to breathe. While the causes of ALS are largely unknown, most cases likely arise through a combination of genetic factors and environmental stress.

A small number of ALS cases are due to known genetic mutations that are transmitted through familial gene inheritance (familial, or fALS). The genetic mutations known to cause ALS have been transferred to cells and animal models so that the disease may be studied more extensively in the laboratory. Cells expressing ALS mutations degenerate similarly to the motor neurons in patients, and can be used to identify cellular mechanisms of disease and for testing possible therapies. Mice with ALS mutations develop the same motor neuron disease as humans, including weakness and eventual death, and are important for studying the effects of treatments on disease onset and progression.

Most ALS cases, however, are without a known genetic mutation (sporadic, or sALS). Probable causes include: imbalances of the neurotransmitter glutamate, stress related to aging or other environmental factors, loss of necessary support from surrounding cells in the spinal cord and at neuromuscular contacts, and interference with structural proteins in motor neurons. Each of these problems likely plays a role in the disease process, but currently a clear understanding of the causes of sALS is lacking.

Investigators are continuing to uncover other contributors to the development of ALS. Because of the likelihood that multiple factors come together to cause ALS, we believe multiple simultaneous approaches that target many aspects of motor neuron degeneration will be essential for the effective treatment of ALS.

Current research projects by PNR&D investigators:

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