The researchers' findings, published in the April 1 issue of the Journal of Neuroscience, may offer the first detailed look at how the devastating disease starts and could lead scientists to a way to treat this currently incurable disease.
John Weiss, professor of neurology and co-director of the UCI Muscular Dystrophy Association/ALS center at UCI Medical Center, and graduate student Shyam Rao found that an important neurotransmitter induces the production of molecules called "free radicals" in nerve cells affected by ALS. Along with degrading motor nerve cell function, the free radicals can exit these cells and disrupt function of surrounding support cells that regulate levels of the neurotransmitter. When disrupted, support cells lose their ability to maintain normal neurotransmitter levels. This causes neurotransmitter levels to rise even higher, causing more production of free radicals and leading to a vicious cycle of accelerating motor nerve cell injury.
Weiss' team also found that the neurotransmitter, called glutamate, induces the production of free radical compounds only in motor nerve cells, sparing other nerve cells that control senses and other body functions. In addition, they found that when the free radicals exit the motor nerve cells, they disrupt the surrounding support cells, called astrocytes, which regulate glutamate levels.
"Patients with Lou Gehrig's develop symptoms very quickly," Weiss said. "This study possibly offers the first glimpse of what likely happens at early stages of the disease, setting a course for possible new and effective treatments."
Weiss believes the new model explains why previous studies found that ALS damaged support cells and motor nerves cells were nearly always close together.
"It also helps explain why the disease, once started, can progress so rapidly," Weiss said.
The researchers are now looking at how this new view of ALS may result in better treatments.
ALS degrades nerve cells that control body movement, resulting in progressive paralysis and death. Remarkably, nerve cells important for thinking and sensation are spared. Each year in the United States, about 4,600 people are diagnosed with the disease. Current treatments do not reverse the course of the disorder but only help relieve its symptoms. The disease, discovered in 1869, was named after the legendary baseball player after he died from ALS in 1941.
The UCI MDA/ALS center was recently established with support from the Muscular Dystrophy Association. The center conducts basic research into the mechanisms that lead to disease, which eventually could be used to provide advanced care for people with ALS and other movement disorders. In addition, the center is a resource for state-of-the art treatments for people suffering from these diseases.
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