Washington, D.C., June 10 -- Researchers at the University of Pittsburgh Medical Center (UPMC) have successfully controlled incontinence in an animal model of diabetes using a modified herpes virus to shuttle a therapeutic gene into damaged bladder nerves. The results, which demonstrate the feasibility of this approach in humans, could eventually benefit the more than half of all diabetics who suffer nerve damage that renders them permanently unable to urinate normally. The findings are being presented June 10 at the annual meeting of the American Society of Gene Therapy in Washington, D.C.
"This study provides the first evidence that we can repair visceral nerves and improve bladder function," said William Goins, Ph.D., assistant professor of molecular genetics and biochemistry at the University of Pittsburgh School of Medicine.
Diabetes causes a number of complications, including damage to sensory nerves that supply various tissues. Lacking sensory nerve input to the bladder, someone with diabetes cannot sense when it's time to urinate. As a result, urine backs up, causing the bladder to enlarge. The swollen bladder, which often becomes infected, is untreatable except with catheterization.
Because patients with diabetes do not have a sufficient amount of a substance called nerve growth factor (NGF), which heals injured nerve cells, the UPMC researchers surmised that delivery of the gene for NGF could provide a potential treatment for this form of incontinence.
"We are encouraged that our study may soon translate into real clinical benefit for diabetic patients," said Michael B. Chancellor, M.D., associate professor of urologic surgery at the University of Pittsburgh School of Medicine.
The UPMC team capitalized on herpes' natural ability to infect nerve cells. They placed the gene for NGF inside a herpes vector modified to be harmless. Then the team injected the NGF gene-bearing herpes vector into the bladders of rats with experimentally induced diabetes. Another group of diabetic rats, which served as controls, received an injection of the herpes vector alone. Four weeks after the gene transfer, investigators looked at some of the rats and found that the NGF gene was active in the bladder of those rats that received it.
Ten weeks later, the scientists found differences with respect to bladder function between the remaining groups of rats. Those diabetic rats that received the herpes vector with the NGF gene voided small amounts of fluid each time they urinated and had bladders half the size of control diabetic mice, which released large volumes of urine each time.
"This evidence really suggests that the introduced NGF gene effectively repairs the bladder nerve, allowing animals to sense when they need to urinate. If we can reproduce these results in diabetic people, we possibly could prevent many disease complications down the road," added Dr. Goins, who suggested that the same gene therapy approach could be used to deliver the NGF gene to nerves elsewhere in the body that are damaged due to diabetes.