Gene Therapy Shows Potential In Treating Diabetic Polyneuropathy

Ruzanna Harutyunyan's picture

Intramuscular injections of vascular endothelial growth factor (VEGF) gene show promise for improving neuropathic symptoms in individuals with diabetic polyneuropathy, a condition most commonly affecting diabetics who have had the disease for many years. These findings were presented in April at the American Academy of Neurology Annual Meeting in Seattle.

Symptoms associated with diabetic polyneuropathy include loss of sensation and pain in the legs and feet, weakness, and imbalance. Due to loss of sensation, the development of ulcerations on the feet often go undetected, potentially resulting in amputation, a procedure 15 times more prevalent in diabetics.


Study participants who received the VEGF gene injection had improvement in sensory symptoms and pain, though not in many other characteristics such as nerve conduction tests. “Most patients had fairly severe neuropathy and the expectation for improvement was therefore not high” said Allan Ropper, MD, executive vice chair of the Department of Neurology at Brigham and Women’s Hospital (BWH).

Preclinical studies using animal models have shown that injecting VEGF into the muscle adjacent to nerve trunks can improve clinical function, blood flow in the nerves, and electrophysiological function.

Thirty nine patients were randomly chosen to receive three sets of intramuscular injections of plasmid VEGF in one leg while 11 patients received a placebo in one leg. The injections were given at eight standardized sites adjacent to the sciatic, tibial, and peroneal nerves. Six months after treatment, participants receiving the VEGF injection had greater improvement in symptoms in the injected leg than those receiving the placebo.

In this study, the investigators used a form of the gene that is active without packaging it in a virus, offering a major advantage in safety. “The study shows that this form of gene transfer therapy can be performed relatively safely but further investigation using a larger study group is needed before it can be introduced as a mainstream diabetes therapy,” said Dr. Ropper, noting that this study was limited by its small size and rigid participation criteria.