GROWTH FACTOR MAY LINK
TWO PARALYZING DISORDERS

TUCSON, Ariz., March 4, 2004 — Vascular endothelial growth factor, otherwise known as VEGF, may be a surprising link underlying amyotrophic lateral sclerosis (ALS) and spinal-bulbar muscular atrophy (SBMA), the Muscular Dystrophy Association announced today.

ALS, also known as Lou Gehrig’s disease, is a rapidly progressive disease in which the motor neurons — nerve cells that control muscles — are lost, with resulting paralysis of all voluntary muscle. MDA-supported researchers found last summer that variations in the VEGF gene are apparent risk factors for the disease.

In about 90 percent of cases of ALS, there is no family history, and the cause is unknown.
SBMA, also known as Kennedy’s disease, is a less rapidly progressive but similarly paralyzing disease. It was found by MDA-supported researchers in 1991 to be caused by a flaw in the androgen receptor gene on the X chromosome.

In today’s issue of the journal Neuron, MDA-supported investigators Albert La Spada of the University of Washington in Seattle and Lisa Ellerby of the Buck Institute in Novato, Calif., report on a mechanism by which the flawed androgen receptor may cause SBMA.
They found that the abnormal androgen receptor, itself a protein, sticks to and interferes with a binding protein, and that this binding protein is needed for the manufacture of VEGF. The result, a deficiency of VEGF, is likely responsible for the loss of motor neurons.

To conduct their experiments, they developed mice with exactly the same type of genetic defect for SBMA that’s found in humans. Research suggests experiments with these mice and ALS-affected mice are needed to see whether delivering VEGF to the nervous system can save motor neurons.

“We cannot exclude involvement of other factors or genes at this time,” La Spada said, “and further work is ongoing to determine if VEGF delivery to our mice will be sufficient to prevent and/or reverse their disease.”

But, he continued, “One distinct possibility is that all motor neuron diseases share interruption of the VEGF axis as part of their pathogenesis, an intriguing notion that, if true, could have dramatic implications for treatment.”

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, call (800) 572-1212 or visit www.mda.org.