MILWAUKEE, Wis. - For the first time, experiments in rats suggest that gene therapy may prevent impotence for men having prostate cancer surgery and may even be able to restore sexual function for men who have lost it.
As important as that is for cancer surgery, the technique also shows promise for a much bigger problem: reversing impotence caused by diabetes, radiation treatments and a variety of other conditions, researchers say.
Even if the gene therapy alone doesn't restore sexual function, it may improve nerves enough for Viagra to be able to help such men regain the ability to have sex.
"Viagra doesn't work unless you have intact nerve tissue," and there's often not enough left after prostate surgery for the drug to do any good, said David Jarrard, chief of urologic surgery at the University of Wisconsin-Madison.
Jarrard was not involved in the gene therapy work but is among several dozen surgeons around the country trying new techniques, such as nerve grafts, to keep men from becoming impotent from prostate surgery.
"Erectile dysfunction is such a huge disease, and Viagra has sort of brought it out of the closet," said Michael Chancellor, a prostate cancer surgeon at the University of Pittsburgh Medical Center who led the gene therapy experiments and reported on them recently at an American Urological Association meeting in Chicago.
"We're going in and directly repairing the nerve through gene therapy," he said. "It offers tremendous hope."
Other labs are doing similar work, which already "has clearly documented 'proof of concept' for the utility of gene therapy for the treatment of erectile dysfunction," concludes a review recently published in the journal Urology.
Prostate cancer is the most common cancer among men and the second leading cause of cancer deaths in men in the United States. If a man is young enough to stand it, an operation called a prostatectomy, or removal of the prostate, is recommended because studies show it offers the best chance of curing the cancer and keeping it from coming back. Between 60,000 and 80,000 American men have this surgery each year.
"Prostatectomy is the gold standard, but a lot of men are afraid of it. They hear that if they have it they're going to become impotent or incontinent," Chancellor said.
Impotence often results when one or both of the cavernous nerves, a tangle of nerves that control erections, must be removed to contain the cancer. In such situations, Jarrard and other surgeons have been trying to move a nerve from the foot into the groin to allow men to have an erection.
But in many other cases, the cavernous nerves aren't removed but are traumatized during cancer surgery, leaving a man unable to have sex.
"There's always some damage or stretching on the nerve," so gene therapy or other treatments to help repair it are badly needed, Jarrard said.
Chancellor's gene therapy approach aims to fix that by giving patients a gene that causes production of nerve growth factors, so new neural connections can be forged to compensate for damaged ones.
Men will be relieved to know there are many differences between them and rats. One is that removing a rat's prostate doesn't cause the erectile problems it does in men, so researchers must simulate the damage by partially freezing the rats' cavernous nerves.
Next, they use an ingenious way to give the patient the desired gene - enclosing it in a herpes virus that's been modified so it is harmless and doesn't cause illness.
"These viruses travel up and down nerves" and are in the family of germs that cause painful shingles, so they're good at getting inside nerve cells, Jarrard said.
Several dozen rats got injections of one of two growth factor genes, and a control group of animals got shots of a dummy substance. Pressure in the penis - a measure of ability to achieve an erection - was measured four weeks later, and the rats that got the therapy had statistically significant improvement over the control group, Chancellor said.
Ideally, the gene therapy would be given at the time of prostate cancer surgery, or even before it.
"A week or two before surgery you could give a nerve protection factor," Chancellor said.
A second set of tests he led on other rats offers promise for treating other causes of impotence. Diabetic rats were given shots of the growth factor and showed improvement in erections and ability to copulate compared with rats that got placebo shots.
"It gives hope it can help other impotent men," especially the more than 60 percent of diabetics who develop erectile difficulties at some point in their lives, he said.
"This whole area is in evolution," Jarrard said. "It's still very early on."
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