الفهرس 
Physiology of penile erectionOnly 14 pages are availabe for public view
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Abstract
ED is very common among aging men, and it has a variety of possible etiologies, including combinations of factors.
The past decade has seen an explosion of new information on the physiology of penile erection, patho-physiology of ED, and development of new oral agents (e.g., three PDE5-Is) to manage ED.
Many new advances have been made in the last few years in the understanding of the physiology of penile erection. This is critical to our understanding not only of normal physiology, but how these physiological mechanisms are disrupted by diseases leading to erectile dysfunction, which helps establish a strategy for the prevention and treatment of ED.
The molecular and clinical understanding of erectile function continues to gain ground at a particularly fast rate. Advances in gene discovery have aided greatly in working knowledge of smooth muscle relaxation/contraction pathways.
Failure to respond to PDE5-Is in severe cases of ED has caused efforts to develop new treatment alternatives. The application of gene therapy for ED represents an exciting new field.
Broadly defined, gene therapy is the use of recombinant genetic materials (DNA or RNA) to achieve a therapeutic benefit. Gene therapeutics can be applied to organs or cells in vivo or to tissue removed ex vivo and subsequently returned back to the patient after the cells have been genetically modified. Subsequently, urologic applications of gene therapy are numerous.
Gene therapy is a potential means to correct cell abnormality through the introduction of genetic material which may lead to a therapeutic benefit. DNA is transferred into cells using a vector. This vector can be synthetic or viral. A variety of vectors has been used in gene therapy trials in urology.Different host responses and time course of gene expression can occur depending on the type and size of the vector.
Viruses have evolved to transfer their DNA to cells, and so, it can be used in gene therapy. for safety reasons viral vectors may be ‘replication deficient’, i.e. unable to generate further viral particles after initial infection.
Although preclinical studies have highlighted the application of local gene therapy as a viable treatment option for ED in diverse pathologic conditions including diabetes, ageing, hypercholesterolaemia, and cavernous nerve injury, this therapeutic approach still requires more clinical studies in humans.
A simple concept for gene therapy for ED is that only a very small alteration in the balance between contracting and relaxing stimuli can cause significant effects on cavernous and penile arterial vascular smooth muscle tone.
Gene therapy strategies for ED have focused on the Nitric oxide (NO) / Soluble guanylate cyclase (sGS) / Cyclic guanosine monophosphate (cGMP) pathway. All three NO synthase(NOS) isoforms, endothelial NOS (eNOS), neuronal NOS (nNOS; penile nNOS [PnNOS] is the penile specific variant of (nNOS), and inducible NOS (iNOS), have been used for gene therapy to modulate erectile response.
Recent improvements in carrying genes or proteins into the corpora cavernosa that offer longer gene-transfer efficiency, higher levels of expression of the transduced gene, and little or no immunogenic reactions using plasmid vectors or cell-based therapies (i.e., stem cells) represent important therapeutic parameters in developing gene therapy for safe application of ED.
Recent clinical studies using the maxi-K channel for the improvement of erectile physiology shows great promise and we look forward to long-term efficacy data in current clinical trials using this molecular target.
Gene therapy for ED represents a viable future treatment option for urologists treating ED and will be used in the near future for patients with severe ED unresponsive to current first-line therapies.