Mouse Study Suggests Brain Is Damaged Early in Lou Gehrig's Disease

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TUESDAY, Nov. 11, 2014 (HealthDay News) -- Muscle-controlling nerve cells in the brain may be damaged earlier in Lou Gehrig's disease than previously thought, a new mouse study suggests.

The findings may lead researchers to shift their focus on the origins of the neurological disease -- also called amyotrophic lateral sclerosis (ALS) -- from the spinal cord to the brain's motor cortex, according to the researchers from Cedars-Sinai Medical Center's Regenerative Medicine Institute in Los Angeles.

ALS is an invariably fatal disease that causes muscle weakness, paralysis and, ultimately, respiratory failure.

"In this study, we show the exact progression of ALS in animals that have an inherited form of the disease, and we expose the brain's significant role in initiating the disease process thought previously to originate in the muscle or spinal cord," study senior author and institute director Clive Svendsen, said in a Cedars-Sinai news release.

"We did this by selectively removing the disease-causing mutation just from the brains of ALS animals, and found that this alone had a big impact on disease initiation and progression," he added.

The study was published Nov. 12 in the Journal of Neuroscience.

"We found that spinal motor neurons [nerve cells that control muscles] die before symptoms begin and before nerve damage occurs between the spinal cord and the muscles," Svendsen said.

"In fact, motor neuron death starts in the spinal cord and radiates out to the muscle and the brain over time," he explained. "Motor neurons in the brain are not lost until the final stages of the disease, but starting very early in the process they appear to exist in a dysfunctional form."

"When we suppressed the ALS mutation in the brains of animals, onset of the disease was delayed, the animals lived longer, spinal motor neurons survived longer, and the neuromuscular junctions stayed healthy longer," he added.

Study first author Gretchen Thomsen, a scientist in Svendsen's laboratory, added that, "It is likely that dysfunction at a cellular level, without cell death, goes undetected for years prior to symptom onset and clinical diagnosis."

"It is imperative that we identify patients at high risk of developing ALS and devise and initiate treatments that can intervene before an irreversible cascade of motor neuron circuitry failure sets in," Thomsen added.

Scientists note that research involving animals often fails to produce similar results in humans.

More information

The U.S. National Institute of Neurological Disorders and Stroke has more about amyotrophic lateral sclerosis.