April 1, 2001 -- Move over, Viagra: A team of researchers has found that an experimental form of gene therapy can restore over-the-hill male rats to the sexual potency -- as measured by their ability to have erections -- of studly young rats just a third their age. The therapy was described at the annual Experimental Biology meeting in Orlando, Fla.
Although the therapy is far from being ready for prime time in humans, it has potential as a long-acting treatment that could help to restore youthful vigor to men with erectile dysfunction, report Trinity Bivalacqua and colleagues from Tulane University in New Orleans and Johns Hopkins University in Baltimore.
In their study, the researchers injected into the penises of aged rats a cold virus modified to carry a gene that helps blood vessels in the penis to expand and fill with blood, one of the key steps necessary to creating and sustaining an erection.
"We looked at the physiology, asking is this going to help these animals get better erections, which it did," Bivalacqua, a medical student at Tulane University, tells WebMD.
Erections are controlled by a complex series of events involving nerves and the signals they carry, as well as hormones and other substances that control the expansion of blood vessels, so it's not surprising that any one of several defects or disruptions of one of the mechanisms involved in sexual performance in men can result in erectile dysfunction.
One method for treating erectile dysfunction has been through direct injection into the penis of substances that stimulate the release of chemicals within the penis that control the relaxation of smooth muscle. When smooth muscles surrounding the blood vessels in the penis relax, they allow more blood to enter, thereby causing an erection. Drugs like Viagra work by interfering with an enzyme that would otherwise prevent relaxation of smooth muscle.
Unfortunately, penile injections and Viagra are one-shot deals and need to be repeated every time a man with erectile dysfunction wishes to have sexual intercourse.
To see whether they could create a longer-lasting treatment for erectile dysfunction, Bivalacqua and colleagues injected into the penises of aged male rats a harmless cold virus, called an adenovirus, that had been modified to carry a gene for an important neurotransmitter, or chemical messenger, involved in erections.
Five days after the injections, the rats underwent nerve stimulation to simulate a normal erection, and their responses were compared with those of other rats one-third their age. The researchers found that older animals that received the adenovirus had erectile responses comparable to those of young rats. In contrast, older rats injected with a different gene not associated with erectile function had no significant improvements in function.
The researchers also found evidence that the virus continued to be present in penile tissue for up to 30 days, suggesting that the therapy, if found to be safe and effective in humans, could be delivered once a month rather than before every episode of sexual intercourse -- no doubt a welcome prospect to men who are squeamish about the idea of penile injections.
But a urologist who studies gene therapy for erectile dysfunction tells WebMD that there are several drawbacks to using adenoviruses as carriers for genes.
"As a strategy in humans, I think adenovirus has some drawbacks in that it's inflammatory, and usually repeated doses will cause [an immune system reaction]. I think we need to keep trying different genes, and we also need to start looking at long-term strategies for gene expression, because these are [temporary] and won't be permanently incorporated into the penis," says Hunter Wessells, MD, associate professor of urology at the University of Washington School of Medicine in Seattle.
Craig F. Donatucci, MD, a urologist who specializes in research and treatment of erectile dysfunction at Duke University Medical Center in Chapel Hill, N.C., tells WebMD that "conceptually it makes sense, because you fix the problem, but then you have the issue about the dangers of [adenoviruses]."
Donatucci points to the 1999 death of a patient at the University of Pennsylvania who was undergoing experimental gene therapy with an adenovirus for correcting a lifelong metabolic disorder. "If you're talking just about erectile failure, what's your safety level? Where do you set that?" he asks. "From a general philosophical viewpoint, it's very attractive to think of gene therapy in the future, putting in some form of gene therapy, but realistically, it's a long way from happening."