Erectile dysfunction (ED) is frequently associated with injury to the cavernous nerve sustained during pelvic surgery and is the repeated inability to achieve or maintain an erection necessary for sexual intercourse. Recovery from ED that occurs after radical prostatectomy takes a long period of time, even if a patient receives a nerve-sparing procedure.
To facilitate the cavernous nerve regeneration process, University of Pittsburgh researchers led by the McGowan Institute faculty member Joseph C. Glorioso III, PhD, and the School of Medicine’s Joel Nelson, MD, employed a gene therapy approach in rats. The team used herpes simplex virus (HSV) vector-mediated neurotrophic factor gene transfer with vectors expressing either glial cell line-derived neurotrophic factor (GDNF) or the GDNF family ligand neurturin. The latter is known to be an important penile neurotrophic factor and contributes to survival and regeneration of cavernous nerve.
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 (HSV without GDNF or neurturin genes) 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.
Because of the variability of symptoms, estimates of the incidence of ED vary but ranged from 15 million to 30 million affected men in the U. S. and 1 in every 10 men in the U.K—around 2.3 million.
Illustration: McGowan Institute for Regenerative Medicine.
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