Researchers from The Ludwig Institute and the University of California, San Diego (UCSD) School of Medicine have discovered that when motor neurons damaged by amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, inappropriately send the wrong signal, immune cells react by killing the messenger.
Their surprising finding provides new direction for therapies to treat ALS. The study, conducted in the laboratory of Don Cleveland, Ph.D., UCSD Professor of Medicine, Neurosciences and Cellular and Molecular Medicine and member of the Ludwig Institute for
Cancer Research, will be published online April 27 in advance of publication in the journal Proceedings of the National Academy of Sciences.
Working in mouse models with an inheritable form of ALS, the researchers found that motor neurons , whose normal role is to trigger muscles to contract , were behaving inappropriately.
"What was very surprising is that the motor neurons themselves are acting partly like immune cells and, as they get damaged, they respond by expressing signaling proteins, which are normally components of the immune system," said Christian Lobsiger, Ph.D., of the Cleveland lab. The researchers theorize that, somehow sensing that something is wrong with the signaling neuron, the immune cells respond to these signals by accelerating the death of the motor neuron. "The immune cells of the nervous system, called microglia , which are themselves impaired in patients with ALS , rush in to clean up damage. But instead of helping the damaged motor neurons, they just make things worse," he said.
ALS is a progressive disease that attacks the motor neurons, long and complex nerve cells that reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body, which act to control voluntary movement. Degeneration of the motor neurons in ALS leads to progressive loss of muscle control, paralysis and untimely death. Estimated to affect some 30,000 Americans, most people are diagnosed with ALS between the ages of 40 and 70. Typically, ALS patients live only three to five years after initial diagnosis.