Researchers have discovered a combination of compounds that may help in the treatment of Peyronie’s disease in its active phase, according to a recent study in European Urology.
After testing 21 substances in an phenotypic screening assay and working with rat models, they determined that the combination of vardenafil [a phosphodiesterase type 5 (PDE5) inhibitor] and tamoxifen [a selective estrogen receptor modulator – SERM] had “synergistic activity” that was more effective than either drug alone.
Peyronie’s disease is thought to be a wound healing disorder that causes areas of fibrous plaque to form around the tunica albuginea of the penis. While benign, Peyronie’s disease can lead to painful erections, erectile dysfunction (ED), and an inability to have penetrative intercourse. Current treatments include surgery and collagenase injections.
Found in Peyronie’s disease plaques, cells called myofibroblasts are involved with the development of fibrosis. Inhibiting the transformation of these cells could prevent fibrosis.
With these points in mind, the researchers investigated whether compounds thought to be effective for Peyronie’s disease could inhibit myofibroblast transformation.
Using a phenotyping screening assay designed to measure myofibroblast transformation, they tested 21 compounds that have been “suggested to be efficacious in vitro, in vivo animal, and human studies of [Peyronie’s disease.]” Tunica albuginea samples were collected from patients who had had surgery for either Peyronie’s disease or penile cancer.
They found that only two drug types – PDE5 inhibitors and SERMs – showed significant inhibition of myofibroblast transformation.
The two drug classes were then tested in rat models of Peyronie’s disease, using doses that were similar to clinical doses. The researchers determined that “the antifibrotic effect of the combination of vardenafil and tamoxifen was greater than that of each drug alone.”
The authors noted that the combination might be more effective in men who are in the acute phase of the disease.
They acknowledged several limitations. For example, they did not know the mechanism behind the synergistic effect of the vardenafil/tamoxifen combination, but such a mechanism is currently being studied. They also called for the screening of a larger number of compounds.
“These results are likely to lead to further research into the interaction between the two pathways and development of novel therapeutic approaches for the prevention and/or treatment of other fibrotic diseases,” they wrote.
Ilg, Marcus R. et al.
“Antifibrotic Synergy Between Phosphodiesterase Type 5 Inhibitors and Selective Oestrogen Receptor Modulators in Peyronie’s Disease Models”
(Full-text article in press. Published online: October 18, 2018)