No VEGF Variants Found in
North American ALS Patients

A new study of 1,603 North Americans of Caucasian ancestry with and without amyotrophic lateral sclerosis (ALS) has failed to uncover any differences in the gene for vascular endothelial growth factor (VEGF) in the ALS-affected and unaffected study participants.

The finding is consistent with some previous study results, which found no association between ALS and a Dutch population or a London population, but inconsistent with others, which have shown a connection between variations in the VEGF gene and the development of ALS in patients in Belgium, Sweden and Birmingham, England.

Studies in mice also support a role for boosting levels of the VEGF protein, which causes formation of new blood vessels and also has neuroprotective effects, as a treatment for ALS.

The new study included scientists at Northwestern University in Chicago, Duke University in Durham, N.C., and Vanderbilt University in Nashville, Tenn., who published their findings Aug. 8 in Neurology.

They looked at three variations of the VEGF gene in people in their study population to see whether having any of these influenced the development or course of ALS. Almost every participating ALS patient was compared to someone without ALS who shared the same genetic background and/or environment.

A VEGF gene therapy compound for ALS is in development at Oxford BioMedica, a British-based biopharmaceutical company. The company hopes to have the compound ready for clinical trials in 2008.

Sharon Hesterlee, MDA’s vice president for Translational Research, says that she remains open-minded about the possibilities.

“I think what’s key is that, whether or not people with sporadic ALS have VEGF polymorphisms [variants], there may still be a rationale for boosting VEGF levels to try to slow the disease,” she said.

“Finding an associated polymorphism in U.S. patients would have been icing on the cake, but it’s possible that even if decreased VEGF is not a cause of sporadic ALS, increasing VEGF levels may help slow the disease. We do know that artificially decreasing VEGF levels can trigger an ALS-like disease in mice.”

Hesterlee noted that MDA is continuing its support of basic research on VEGF’s possible role in ALS treatment and is considering direct support to industry for the development of ALS gene therapy using VEGF.