See What HealthDay Can Do For You
Contact Us

Genetic Defect Linked to Gehrig's Disease

Vessel problem tied to muscle wasting in mice

TUESDAY, May 29, 2001 (HealthDayNews) -- Gene defects in a protein that helps feed oxygen to muscle cells in mice causes nerve damage that closely resembles the disease that killed Lou Gehrig, new research says.

The baseball great was stricken with amyotrophic lateral sclerosis (ALS), a progressive muscle wasting disorder that typically sets in during adulthood. Up to two in 100,000 Americans develop ALS, which has no effective treatment or cure and usually is fatal within about five years of onset, says the ALS Association.

In the early 1990s researchers found that about 2 percent of ALS cases were linked to flaws in a gene, called SOD1, that helps the body rid itself of renegade oxygen molecules produced by cells in response to lack of oxygen and other stresses.

The latest study, reported in the June issue of Nature Genetics, suggests that at least some, and perhaps the vast majority of the remaining cases may result from problems with a protein called vascular endothelial growth factor (VEGF).

The molecule is a key player in the growth and spread of blood vessels. Through chemical communication with muscle fibers, the genes that generate VEGF can sense when tissue needs more oxygen and promote new vessels to meet that demand.

The researchers, led by Peter Carmeliet of the University of Leuven in Belgium, sought to learn what happens when this feedback system, called the hypoxia-response element, goes awry. Carmeliet's group bred a strain of mice whose VEGF promoter genes were missing the hypoxia-response element and thus were less responsive to calls from muscle cells for more oxygen.

Most of the animals died before or around the time of birth. Those who survived were significantly smaller and grew about 45 percent less rapidly than their litter mates, the researchers say. And as they reached about 5 to 7 months of age, they began showing symptoms of motor nerve problems. They failed to struggle as mice normally do when held in the air by the tail, they couldn't groom themselves properly, they lost mobility, and they developed awkward gaits.

The mice also showed other signs of ALS-like changes, including degeneration of motor nerves, muscle atrophy and the appearance of thread-like nerve growths in the spinal cord and brain stem.

"Our findings indicate that abnormal expression, not function, of VEGF may constitute a previously unknown risk factor for motor neuron degeneration," the researchers write. "A primary cause of ALS may be chronic deficits of VEGF-dependent vascular perfusion" or a direct effect of the protein on motor nerves themselves. Motor neurons are especially sensitive to variations in chemicals in the blood because they're so big and have particularly large metabolic requirements, the researchers say.

Lucie Bruijn, science director and vice president of the ALS Association, calls the discovery "very exciting."

"We have no evidence" that VEGF problems are linked to ALS in humans, Bruijn says. "But it's fascinating because this was not a function that they had assigned to VEGF before. This is the first connection to the motor neurons, and when you knock out this response, it clearly mimics ALS in patients."

In a cautionary note, the researchers say experimental cancer treatments that target VEGF to shrink blood vessels feeding tumors, a process called anti-angiogenesis, "should now be carefully examined" in light of the new findings.

What To Do

To find out more about ALS, visit the ALS Association or the ALS Survival Guide.

For more on anti-angiogenesis, try Yale University or the Urological Sciences Research Foundation.

Read other HealthDay articles about Lou Gehrig's disease.

SOURCES: Interview with Lucie Bruijn, Ph.D., science director and vice president, ALS Association, Calabasas Hills, Calif.; June 2001 Nature Genetics
Consumer News

HealthDay

HealthDay is the world’s largest syndicator of health news and content, and providers of custom health/medical content.

Consumer Health News

A health news feed, reviewing the latest and most topical health stories.

Professional News

A news feed for Health Care Professionals (HCPs), reviewing latest medical research and approvals.