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Chicago--A phase II clinical trial now enrolling patients aims to test the efficacy of an immunophilin ligand in assisting the regeneration of penile nerves following radical prostatectomy.
The trial will test the pharmacotherapy, a derivative of tacrolimus, on approximately 280 men, who will each take four pills four times per day for 3 days before surgery, and will continue for 6 months afterward.
"If this is successful, we may be able to develop the therapy in the form of wafers or polymers and just insert them next to the neurovascular bundles in the pelvis with surgery, without the hassle of patients having to take all these pills. These are extremely motivated men to take all the required pills," said Arthur L. Burnett, MD, professor of urology at the Brady Urological Institute of Johns Hopkins Medical Institutions.
"These ligands did cause nerve-sprouting in petri dishes," Dr. Burnett said at the Johns Hopkins Advances in Genitourinary Health meeting here. "Immunophilins are by definition receptors originally described to exist in immune cells, but we found that they actually exist in nerve tissue at a 50-fold higher concentration."
While the possibility that other classes of pharmaceuticals such as PDE-5 inhibitor drugs could help nerves recover is a great theory with potential, it has not been established, Dr. Burnett said.
Research on the derivative, which is not approved for any use by the FDA, is sponsored by Guilford Pharmaceuticals.
Although the nerve-sparing technique of conducting prostatectomies, which was publicized by Brady Institute researchers in the early 1980s, has reduced the rate of erectile dysfunction following radical prostatectomy, patients want faster results.
"Our patients are demanding that erectile function return within weeks, especially if we use the nerve-sparing technique," Dr. Burnett said. "In the past it was universal that men were rendered permanently impotent following prostatectomy. While innovations are still being made with laparoscopic and robotic approaches, these along with open surgical procedures seek to minimize nerve trauma. We still need to develop novel ways to get the nerves to get their function back faster. There's still always going to be some nerve trauma despite the best surgical techniques."
Johns Hopkins hopes to enroll 60 patients in the multi-institutional trial, having enrolled about 20 as of October 2004, according to Dr. Burnett.
"While I do 15 to 20 radical prostatectomies a month myself, I've only enrolled a few guys a month, because the study excludes patients who are impotent upon going into the surgery, as well as those with other disease conditions such as diabetes or cardiac disease, or those who are over 65, because there's an age-related nerve degeneration."
After the therapy is complete, researchers will follow patients for a year, although it sometimes take a year to two years for potency to return after surgery, he noted.
After completing the three-arm study (high-dose, low-dose, and placebo), researchers hope to report the results by spring of 2006, as well as an earlier interim report.
"On the animal level, we have found that immunophilin ligand therapy may be important as a neuroprotective as well as a neuroregenerative therapy," Dr. Burnett said.
Dr. Burnett has served as a scientific advisor to Guilford Pharmaceuticals, serves as a scientific adviser on the current study, and has been supported in basic science work by the company.