Gene therapy delivery of nerve growth factors reverses erectile dysfunction in mice

Jun 5 2007

Rats with erectile dysfunction, or ED, that were injected with a gene therapy vector containing either of two nerve growth factors were able to regain normal function after four weeks, according to a study conducted by University of Pittsburgh School of Medicine researchers.

These findings are being presented at the 10th annual meeting of the American Society of Gene Therapy, which is convening May 30 to June 3 at the Washington State Convention & Trade Center, Seattle.

ED is the repeated inability to achieve or maintain an erection necessary for sexual intercourse. Because of the variability of symptoms, estimates of the incidence of ED vary but range from 15 million to 30 million affected men in the United States. ED is frequently associated with damage to the cavernous nerve that results from surgery for prostate cancer. Even if a patient receives a nerve-sparing procedure during surgery, recovery from ED after radical prostatectomy may take a long time.

In this study, which was led by Joseph C. Glorioso, III, Ph.D., chair of the department of biochemistry and molecular genetics, and Joel Nelson, M.D., chair of the department of urology, University of Pittsburgh School of Medicine, researchers inserted either the gene for the glial cell line derived neurotrophic factor (GDNF) or the GDNF family ligand (neurturin) into a genetically engineered herpes simplex virus (HSV). They then injected either of the recombinant viruses into the damaged cavernous nerve of rats. GDNF is an important nerve growth promoter and has been shown in other studies to contribute to survival and regeneration of penile nerves. Neurturin also is a nerve growth factor closely related to GDNF. Control mice received only the virus without the GDNF or neurterin genes inserted.

Four weeks after the treatment, rats administered HSV-GDNF exhibited significant recovery of intracavernous pressure (ICP) and systemic arterial pressure (AP) compared with rats treated with the control virus or untreated mice with ED. Rats treated with HSV-neurturin also exhibited significant recovery of ICP and AP compared with the control or untreated mice at four weeks after treatment. Fluorescent protein studies also showed that the delivered genes had been effectively incorporated into the target nerve cells.

According to Dr. Glorioso, HSV delivery of GDNF or neurturin presents a potentially important new approach for the treatment of ED. "Because the herpes virus persists in the nerve cell for as long as it is alive and nerve cells typically do not reproduce, this represents the first-ever demonstration of a long-term treatment for ED that does not rely on the chronic administration of drugs that can have potentially harmful side effects," he explained.