Scientists today presented provocative pre-clinical research results indicating that erectile dysfunction (ED) can be prevented following radical prostatectomy. The findings were announced at the Prostate Cancer Research Program?s (PCRP?s) Innovative Minds in Prostate Cancer Today (IMPaCT) conference in Orlando, Fla.?a gathering of the nation?s most prestigious scientists, clinicians, and consumer advocates in prostate cancer research.

ED is a major risk for men with prostate cancer who undergo radical prostatectomy, an operation to remove the prostate gland and some of the tissue around it. Many men may feel reluctant to undergo the surgery because there is such a high risk of ED.

?Our hope is that these PCRP-funded findings will help reduce the potential complications of prostate cancer treatment and improve survivor quality of life,? said Navy Captain Melissa Kaime, MD, Director of the Congressionally Directed Medical Research Programs (CDMRP), which supports the IMPaCT conference.

Damage to the cavernosal nerve, which innervates the penile smooth muscle and arteries responsible for penile erection, during radical prostatectomy causes the most prevalent form of ED, named corporal veno-occlusive dysfunction (CVOD), or venous leakage. Venous leakage ED occurs when the penile smooth muscle does not dilate sufficiently upon sexual stimulation to tightly compress the draining veins, and the blood that accumulates in the penis to induce the erection is not retained.

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Long-term daily administration of phosphodiesterase 5 inhibitors
Through several different lab-tested models that mimic risk factors for ED, scientists investigated damage to the cavernosal nerve in the laboratory rat to determine whether venous leakage caused by the procedure may be prevented by a long-term daily administration of phosphodiesterase 5 inhibitors (PDE5i). PDE5i are a class of drugs, such as the well-known Viagra, Cialis, or Levitra, which prevent the enzyme named PDE5 from destroying the compound cGMP. cGMP works to facilitate an erection by dilating the penile smooth muscle to permit great blood flow. The PDE5i class of drugs is currently used in the clinic to induce an erection on demand, but they are not aimed to cure ED.

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Additionally, researchers worked to determine whether administering generators of nitric oxide, which mediates penile erection by causing the production of cGMP, alone and in combination with muscle-derived stem cells (MDSC) might prevent ED. These stem cells may help the regeneration of the penile smooth muscle that is partially lost due to the nerve damage.

Early long-term continuous treatment
Investigators concluded in an animal model that an early long-term continuous treatment with PDE5i, as opposed to current on-demand regimens, have a high probability of preventing the occurrence of ED after cavernosal nerve damage because it protects the penile smooth muscle. Results also showed that MDSC prevented CVOD, although this effect was independent of stimulation by treatment with nitric oxide generators.

‘Penile rehabilitation’
?Our results provide a scientific basis and support for the emerging clinical interest in preventing or ?curing? ED with a long-term sustained use of PDE5i before or after radical prostatectomy, rather than merely using them palliatively to facilitate an erection at will, in a modality called ?penile rehabilitation?,? said Nestor Gonzalez Cadavid, PhD and Professor of Medicine, Charles R. Drew University of Medicine and Science. ?As recently reported in several publications from our group, mainly funded by PCRP, dilation of the penile smooth muscle is the mechanism of this long-term action that protects the penile smooth muscle and avoids tissue fibrosis. This is different from the mechanism that induces an erection at will, which is currently the main reason for prescribing PDE5i for ED.?

Dr. Gonzalez-Cadavid emphasized that this can only be translated to patient treatment if the concept is proven in ongoing clinical trials, and if so, it should be supervised by a physician. The use of stem cells alone or in combination with PDE5i is promising in experimental animals, but its clinical application may be more remote.

In addition to this study, the IMPaCT conference provides a broad overview of the field of prostate cancer research, while highlighting the important contributions that PCRP-funded investigators have made. The PCRP is committed to improving early detection and diagnosis, developing new and effective therapies and prognostic tools, and improving the quality of life for all persons affected by prostate cancer.

The study was conducted by researchers from University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, Biomedical Research Institute at Harbor-UCLA Medical Center, and Charles R. Drew University of Medicine and Science.

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