***Trost Commentary and Key Take-Home Points***
This is a great commentary which highlights the significant need that we have for better medications to treat Peyronie’s Disease. For decades, dozens of medicines, herbals, topicals, and energy types of treatments have been used to try to treat Peyronie’s Disease. And, with few exceptions, none of them have showed any true promise in treating the condition. This is not an issue which is unique to Peyronie’s Disease, as many other fibrosing types of conditions have suffered the same limitations. This article discusses many of the reasons why medications have traditionally not been very effective and emphasizes how newer technologies may ultimately help to identify or develop new drugs which may be used in the future. But, at the present time, the answer to the question, “what role do pharmaceuticals play in the treatment of Peyronie’s Disease” is, ‘not much (unfortunately).’
Introduction
Peyronie’s disease is a connective tissue disorder affecting the tunica albuginea, initially causing pain during erection. Eventually, the disease stabilizes resulting in less pain but a penile curvature that can lead to erectile dysfunction, psychosocial issues and inability to have intercourse. Treatment options include surgery or injections of collagenase clostridium histolyticum. There is not sufficient evidence of efficacy of other treatments, like mechanotherapy and iontophoresis and no treatments have been approved as preventative or effective options in the early stage of the disease.
The etiology of Peyronie’s disease remains unknown, though it is thought to be caused my micro-traumas to the penis. Research has revealed connections to an imbalance between the extracellular matrix anabolism and myofibroblast apoptosis, in addition to a persistent immunological signature involving macrophages. This inflammation has many pathways and complicates the process of developing efficacious drugs that are antifibrotic.
Drug discovery and development have classically been made with a target-based approach, but there has been an upswing in the phenotypic screening approach since researchers have suggested it is more biologically relevant. An example of this approach in action was a study testing 21 compounds as Peyronie’s disease treatments and phosphodiesterase type 5 inhibiters (PDE-5is) and selective estrogen receptor modulators (SERMs) were found to have a synergistic anti-fibrotic effect.
Research for other fibrotic diseases, such as liver, pulmonary and kidney, have found successful treatments by describing their numerous pathways and diverse targets. While informative of the fibrotic process in Peyronie’s disease, it is not given that the treatments used for other fibrotic diseases will affect or treat Peyronie’s disease in the same way.
Conclusion
In order to develop more efficacious drugs for Peyronie’s disease, better clinical trials, standardized methods and demographic similarities will provide quality data about the drugs being studied. Paying particular attention to the stage of the disease and progression of the plaque formations in the inclusion/exclusion process will help make clinical trials more accurate, as will the use of a clinically validated molecular biomarker.
References
U Milenkovic, Mm Ilg, S Cellek & M Albersen (2019) What role do pharmaceuticals play in the treatment of Peyronie’s disease and is there a need for new emerging drugs?, Expert Opinion on Emerging Drugs, 24:1, 1-4, DOI: 10.1080/14728214.2019.1591370
https://www.tandfonline.com/doi/full/10.1080/14728214.2019.1591370