Gene therapy has already proven to be a fairly effective and safe method of treating many diseases, but remains inaccessible for widespread use in medical practice, in particular, in urology for the treatment of erectile dysfunction. Today, gene therapy is used primarily to treat monogenic diseases inherited in an autosomal recessive manner. However, there is potential for gene therapy to be extended to other conditions, such as erectile dysfunction. Despite the high success rate of erectile dysfunction treatment with drugs in the PDE5 inhibitor category, a certain number of patients do not respond to this therapy, as well as to other medications used to treat ED.
Today, gene therapy has already been proposed as one of the potential new treatments for erectile dysfunction resistant to PDE5 inhibitors. The research is at the preclinical stage and is aimed at studying the potential of gene therapy for erectile dysfunction cases caused by various reasons, such as aging, diabetes and damage to the cavernous nerve. The focus of the researchers is on genes involved in the synthesis of nitric oxide. Also under consideration are genes encoding various types of neurotrophic factors that can enhance nerve regeneration. This may be relevant for the neurogenic type of erectile dysfunction caused by diabetes or damage to the cavernous nerve. Another area that scientists are paying attention to is the K+ channel genes, which functionally enhance the relaxation of the smooth muscles of the cavernous bodies of the penis.
The penis is a convenient tissue target for gene therapy because of its external location and accessibility, the ubiquity of endothelial-lined spaces, and low level of blood flow, especially in the flaccid state. Gene therapy approaches are focused on a number of signaling pathways that are crucial for penile erection, such as nitric oxide/cyclic guanosine monophosphate, RhoA/Rho-kinase, growth factors, ion channels, peptides, and control of oxidative stress.
Gene therapy for ED has been studied for the past decade. However, there are significant safety concerns that have delayed gene therapy trials from moving into human clinical trials. The greatest promise for gene therapy for ED so far comes from studies using non-viral gene therapy for the Ca2+-activated BK (Max-K) channel.
Despite the fact that the introduction of PDE5 inhibitors into medical practice at the end of the 20th century led to a stunning breakthrough in the treatment of erectile dysfunction, the demand for new therapeutic and surgical options for the treatment of ED continues to grow. This is due to both the increasing proportion of elderly men in the population and the growing percentage of patients who don’t respond to standard therapy. Surgical treatment is associated with many complications and the fact that few patients decide to undergo it. Therefore, non-surgical treatment methods are extremely relevant. This determines the relevance of studying the potential of gene therapy in the treatment of erectile dysfunction. However, there are many problems and obstacles on the way to the implementation of such methods, including possible accidental expression of transgenes.
Overall, gene therapy for erectile dysfunction represents a promising treatment option, especially for men with severe erectile dysfunction who are refractory to established first-line treatments such as PDE5 inhibitors. The need for effective ED therapies in difficult-to-treat patients has encouraged investigators to seek novel modalities for the treatment of ED. Recent preclinical and clinical trials have demonstrated that gene therapy strategies may be feasible for these purposes.
