A futuristic treatment for an age-old problem
Back in the early ’90s, Arnold Melman and George Christ were mocked when they suggested using gene therapy to cure impotence. After all, the futuristic form of medicine requires an often-dangerous intervention into the genetic code. At the time, gene therapy was inspiring dreams of curing cancer, AIDS and other debilitating diseases, not something as “frivolous” as erectile dysfunction.
Melman and Christ saw some vindication earlier this month when the results of their first human study ran in the December issue of the journal Human Gene Therapy.
And so, the dream of gene therapy might find its first widespread application in helping people have sex.
Melman, a urologist, says he realized years ago that impotence often stems from a breakdown of communication between cells.
Here’s how it works: To get an erection, the smooth muscle cells in the penis must communicate with each other. A gene called hMaxi-K is activated, creating a protein that goes out to the cell membrane and opens a window, allowing potassium to flow out of a cell. The exiting potassium ions leave the cells with a net negative charge, which triggers yet another protein to close another window to keep calcium ions in.
The closing of that calcium channel prompts the smooth muscle cells to relax, which then lets blood flow in and get trapped. When a man doesn’t have an erection, the muscle cells are contracted.
It’s more complicated than most people appreciate, he says.
One way to intervene, he and colleague Christ realized, would be to get more of the gene hMaxi-K into the penis muscle cells, thus helping prime the pump.
But over the years other researchers discovered the tragic hazards of editing the human genetic code.
Some, such as James Wilson at the University of Pennsylvania, were infusing patients with modified cold viruses carrying “corrective” genes. In 1999 that technique led to a fatal immune reaction in an 18-year-old being treated for a nonfatal genetic disease.
Other viral carriers spliced new DNA directly into patients’ existing genetic code in a way that triggered cancer.
“But this is not that kind of gene therapy,” says Christ, a professor in the department of regenerative medicine at Wake Forest University in North Carolina. He and Melman weren’t using viruses but instead injecting so-called naked DNA into cells, where it would help make more of the erection protein.
Other researchers are using a similar technique to deliver vaccines without the risks associated with viruses.
After years of treating rats, Melman, Christ and collaborators got FDA approval to treat 11 men who had been completely impotent for months and didn’t respond to Viagra-type drugs. These men got a shot of the DNA directly into the tissue along the length of the penis that fills with blood during erection. Christ insists it really doesn’t hurt.
The first volunteers got a low dose, designed to test safety. They reported no side effects, and two said it put them back in action.
Isn’t gene therapy a little too risky and invasive for something like erectile dysfunction? “You’ve obviously never had the problem,” says Melman, who assured me they had no shortage of willing volunteers.
“It’s easy to laugh about it or say it’s trivial,” says bioethicist Art Caplan, “but people kill themselves because they’re impotent.”
Beyond that, Caplan says, this research will help in understanding how to harness gene therapy while using it on an organ that’s pretty accessible.
And whatever knowledge is gained could bring all those other scientists a little closer to modifying the book of life to cure cancer, AIDS and more.
Faye Flam’s Carnal Knowledge column appears Sundays in The Seattle Times.
Copyright © 2006 The Seattle Times Company
