April 24, 2014

   A Publication of the James Buchanan Brady
   Urological Institute Johns Hopkins Medical Institutions

Volume 1, Winter 2005

Protecting the Nerves, Restoring Potency Sooner

Just as a knight heading off to battle needs armor, or a child needs a sweater on a cold day, nerves sometimes need extra protection, too. This is especially true in the case of the fragile nerves involved in erection in men who undergo radical prostatectomy. No matter how meticulous the surgeon, the trauma of surgery—any surgery—is hard on the nearby nerves. Even in the best of cases, says Arthur L. Burnett, M.D., professor of urology, “they sustain some sort of damage, at least temporarily.”

The reasons for this damage—and the specific nature of the nerve injury—remain unclear, but the result for many men is a frustrating delay in the recovery of potency, the ability to have and maintain an erection. In breakthrough work with Hopkins neuroscientist Solomon Snyder, M.D., several years ago, Burnett discovered that rats with nerve injury and erectile dysfunction (similar to that found in men after radical prostatectomy) were helped greatly by the use of a solution containing immunophilins.

The rats treated with an immunophilin ligand—a “jumpstarter” that activates these proteins—showed dramatically less nerve damage, and much greater restoration of function. They had stronger erections, and recovered earlier.

Immunophilins are special healing proteins made by nerve tissue; when a nerve is injured, they rush to its aid, and help repair the damage. The rats treated with an immunophilin ligand—a “jump-starter” that activates these proteins— showed dramatically less nerve damage, and much greater restoration of function. They had stronger erections, and recovered earlier. This and other immunophilin ligands, Burnett says, work by stimulating receptors in nerve tissue “which, in turn, promote healing and recovery in injured nerves.”

Burnett’s first immunophilin solution was a ligand called FK 506, a drug commonly used to suppress the immune system in people who have undergone organ transplants. He and colleagues have since developed even more targeted ligands that don’t affect the immune system, and are just as successful in soothing, protecting, and invigorating these delicate nerves.

Now, in what Burnett calls an example of “true translational research,” a medical therapy that originated in the laboratory has been developed for a clinical investigation that’s currently under way. A new study—the first of its kind—will test this therapy, a neuroimmunophilin compound called GPI 1485, taken in pill form by men after radical prostatectomy. The Brady Urological Institute is one of 13 medical centers in the United States taking part in this clinical trial, sponsored by Guilford Pharmaceuticals, Inc. Men will be randomly assigned either to the drug, or to a placebo; all of the men are required to record their impressions about their functional recovery.

“We hope to be able to report the results from the study within the next year,” says Burnett. “So far, we know that the men have tolerated the drug well, with no major side effects. Any evidence that the drug therapy is effective in enhancing the recovery of erectile function after radical prostatectomy will serve as an important advance in the field, and may also help us develop further neuroprotective interventions in the future.”

 

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