BALTIMOREA single injection of FK506 (Prograf) or a similar immunophilin
drug at the time of surgery might prevent impotence in men undergoing
nerve-sparing prostatectomy for localized prostate cancer, according to
preclinical work reported in Nature Medicine (7:1073-1074, 2001) by Sena F.
Sezen, PhD, and colleagues at the Johns Hopkins Medical Institutions.
The researchers found that a 1 mg/kg intraperitoneal dose of FK506 preserved
90% of erectile function and reduced nerve damage by about half in rats
subjected to nerve damage similar to that seen with nerve-sparing radical
This study has clinical implications for the 80,000 men each year who must
face treatment for localized prostate cancer. Nerve-sparing prostatectomy
techniques had been thought to reduce the incidence of impotence to about 30%,
but the Prostate Cancer Outcomes study, a population-based longitudinal cohort
study, found that 56% of men who were potent before bilateral nerve-sparing
prostatectomy reported being unable to achieve intercourse at 18 or more months
after surgery (JAMA 283:354-360, 2000).
Fujisawa Healthcare, which markets FK506 as an immunosuppressant for
prevention of allograft rejection, has no plans for testing the drug as a
neuroprotectant during prostatectomy. However, senior author Solomon H. Snyder,
MD, told ONI that Guilford Pharmaceuticals will begin trials with NIL-A, a
derivative of FK506 that retains the parent compound’s neurotrophic and
neuroprotective effects but does not suppress immune function. NIL-A is
currently in development for the treatment of Parkinson’s disease.
Dr. Snyder is professor and director of the Department of Neuroscience at
the Johns Hopkins School of Medicine. He is also co-founder and chief
scientific advisor of Guilford Pharmaceuticals.
In addition to Drs. Snyder and Sezen, the research team included Ahmet Hoke,
MD, PhD, and Arthur L. Burnett, MD. Dr. Hoke is assistant professor and
co-director of the Neuromuscular Pathology Laboratory at Johns Hopkins. Dr.
Burnett is in the Department of Urology.