MDA SCIENTISTS FIND POSSIBLE
KEY TO LOU GEHRIG’S DISEASE

TUCSON, Ariz., March 10, 2003 — Research funded by the Muscular Dystrophy Association has homed in on a potential trigger for amyotrophic lateral sclerosis (ALS), a fatal disease that typically has no clear cause.

ALS, also known as Lou Gehrig’s disease, attacks the muscle-controlling nerve cells called motor neurons, causing the muscles connected to them to waste away. There is no cure, and many people with the disease succumb to respiratory failure within three to five years of diagnosis.

A new study published on-line by Nature Genetics shows that genetic defects affecting a supply line within motor neurons can lead to an ALS-like disease.

Researchers based at the National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Md., probed the DNA of a large family from Alabama that has a hereditary motor neuron disease similar to ALS. Their analysis revealed mutations in the dynactin gene, which encodes a protein that helps move nutrients, growth factors and other cargo along axons — the long thread-like appendages of nerve cells.

“This is an important finding because it supports data from animal studies suggesting that defects in axonal transport might play a key role in ALS,” said Sharon Hesterlee, MDA director of Research Development.

Ninety percent of ALS cases are sporadic (having no known cause), and the remaining 10 percent are hereditary. About one-quarter of hereditary ALS can be traced to mutations in the SOD1 gene, but even in these cases, the details of the disease process are unclear.

In a 1999 study, MDA-funded researchers found that mice with SOD1-related ALS show impaired axonal transport before they show signs of weakness. And last year, Erika Holzbaur of the University of Pennsylvania in Philadelphia found that when normal mice are genetically engineered to produce an inhibitor of dynactin, they develop ALS.

Holzbaur, Kenneth Fischbeck and Imke Puls of NINDS, and Robert Brown Jr., director of the MDA/ALS center at Massachusetts General Hospital in Boston, were key authors on the current study.

Studies of dynactin and axonal transport might hold insights into treatments for ALS, Fischbeck said. “If we can further understand this mechanism, hopefully it will lead to a better understanding of how to keep motor neurons alive,” he said.

Mutations in dynactin or related proteins might underlie some forms of hereditary ALS, while other disruptions of axonal transport — perhaps by toxins or infectious agents — might be capable of triggering sporadic ALS, he added.

MDA is a voluntary health agency working to defeat more than 40 neuromuscular diseases through programs of worldwide research, comprehensive services, and far-reaching professional and public health education.

For more information about MDA's research and services, call (800) 572-1717 or go to www.mda.org.