Sexual Problems and Issues - Latest Research

Results Of The First Human Trial For Gene Transfer Therapy For The Treatment Of Erectile Dysfunction

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20 Oct 2006

UroToday.com - Gene therapy for erectile dysfunction, the gene transfer of relevant molecules involved in the regulation of penile erection, has emerged from just an imaginable possibility to an exciting reality.

In this phase I "safety" trial, ion channel gene transfer with hmaxi-K was used as an approach taking advantage of the smooth muscle biology of the penis and the basic exchange of ions that cause penile erection. Nine men with severe erectile dysfunction were enrolled, all showing no drug-related adverse events or intolerability. Amazingly, 2 men achieved sustained functional erection improvement. While further clinical safety and efficacy objectives clearly remain to be met, this study is a major development in erectile dysfunction management.

Editor's note: Gene Therapy is the "Holy Grail" of medicine, curing disease at the molecular level. In this case Dr. Melman's lab is entering a new arena of clinical studies after more than a decade of investigating the role of potassium channels in normal and abnormal erection physiology. The concept here is to improve natural erections by modifying cell to cell signaling responsible for smooth muscle relaxation. This first clinical step is to demonstrate that the vector with the coded information for the maxi-K channel sets up in the penis without causing systemic side effects. The next area of clinical testing will be to evaluate efficacy in men with erectile dysfunction.

Abstract 686; 2006 AUA Annual Meeting (Atlanta, Ga. May 20-25)
Reviewed by UroToday.com Contributing Editor Arthur Burnett, MD
http://www.medilexicon.com/medicalnews.php?newsid=54724∞

Vascular Endothelial Growth Factor (VEGF) Gene Therapy Using A Non-Viral Gene Delivery System Improves Erectile Dysfunction In A Diabetic Rat Model

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21 Nov 2006

UroToday.com - In light of the fact that VEGF has shown to improve overall endothelial and smooth muscle cell dysfunction in models of ED and (ED) decreases the quality of life in more than 70% of diabetic men, the authors investigate the ability to achieve in in-vivo gene transfection of VEGF in the rat model. Diabetes was induced and confirmed with a single injection of streptozotocin. Animals then received intracavernous injection with 10 ug plasmid DNA encoding a fusion VEGF/green fluorescent protein (GFP) complex .

Fluorescence microscopy revealed expression of GFP in all treated animals. Western blot analysis confirmed expression of the GFP/VEGF fusion protein, and RT-PCR confirmed the presence of mRNA transcript within the cavernosal tissue of all treated rats and immunohistochemistry analysis of the cavernosal tissue showed an increased number of smooth muscle cells compared to the diabetic controls The authors concluded that this model achieved in-vivo transfection of VEGF into rat corpus cavernosum using a non-viral gene delivery system. Expression of the transected VEGF leads to an overall improvement of maximal intracorporeal cavernous pressure and smooth muscle content.

Editorial Comments;

This study appears to demonstrate the potential for gene manipulation as a therapeutic modality for Erectile Dysfunction. As opposed to currently available therapies, gene therapy may provide disease specific rather than empiric therapies. Clearly, the rate limiting step is bringing such an approach into clinical trials.
http://www.medilexicon.com/medicalnews.php?newsid=57125∞

Study Of Gene Transfer For Erectile Dysfunction Shows Promise

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03 Dec 2006

The first human study using gene transfer to treat erectile dysfunction (ED) shows promising results and suggests the potential for using the technology to treat overactive bladder, irritable bowel syndrome and asthma, according to the researchers.

"In the small pilot study, this new therapy was well tolerated and safe," said George Christ, Ph.D., senior researcher and a professor at the Institute for Regenerative Medicine at Wake Forest University School of Medicine. "It provides evidence that gene transfer is a viable approach to treating ED and other diseases involving smooth muscle cells."

The results of the study, which included 11 men with ED, are reported online today in Human Gene Therapy. The technology was developed by Christ and Arnold Melman, M.D., when they worked together at Albert Einstein College of Medicine in the Bronx, New York.

Unlike traditional gene therapy, the gene transfer approach being pioneered by Christ and Melman does not change the DNA or genetic code of cells. Instead, small pieces of DNA reach the nuclei of cells and this causes them to increase production of particular proteins. These proteins help relax smooth muscle cells, the type of muscle found in the penis as well as in hollow organs such as the bladder. Relaxing the tissue allows the penis to fill with blood and become erect.

Previous research has shown that more than 50 percent of men between 40 and 70 years old and 70 percent over age 70 may have ED. The new therapy is a potential alternative to oral medications, such as Viagra, which are not effective for an estimated 30 to 40 percent of men with ED.

A possible advantage of gene transfer is that a single treatment could last for months. In the current study, improvements were maintained through the 24 weeks of study.

The study was conducted from May 2004 to May 2006 at Mount Sinai School of Medicine and New York University School of Medicine. Men ranged from 42 to 80 years old with a mean age of 59. Six subjects were white, four were black and one was Hispanic. In half of the subjects, the cause of ED was diabetes or cardiovascular disease - both of which can interfere with the ability of smooth muscle cells to relax.

The primary goal of the study was to determine the safety and tolerability of the new therapy. However, the results also showed that at the highest doses, men reported highly significant improvements in erectile function.

The DNA segments - mixed into plasma - were injected into the corpus cavernosum, expandable tissue along the length of the penis that fills with blood during erection. A variety of clinical and laboratory tests were used to assess safety. In addition, effectiveness was measured using the International Index of Erectile Function scale, a questionnaire that is commonly used to measure ED. Patient responses were validated by their partners.

Researchers identified no safety issues with the treatment. Participants who received the highest two doses had apparent sustained improvements in ED as measured by the questionnaire. The researchers said that a larger study that includes a "control" group treated with a placebo is needed to confirm the safety and effectiveness of the treatment.

Other researchers on the project were Melman, Natan Bar-Chama, M.D., with Mount Sinai School of Medicine, Andrew McCullough, M.D., with New York University School of Medicine, and Kelvin Davies, Ph.D., with Albert Einstein College of Medicine.

The technology is being developed by Ion Channel Innovations (ICI), a development stage biotechnology company, in which Christ and Melman are co-founders and directing members. The therapy is known as ion channel therapy because the proteins it targets are potassium channels, "gates" within cells critical for contraction and relaxation of smooth muscle.

At the Wake Forest Institute for Regenerative Medicine, Christ is continuing to pursue the therapy in collaboration with ICI, and is also exploring the potential of combining gene transfer with traditional oral medications to further increase the clinical utility of the technology. The Albert Einstein College of Medicine at Yeshiva University owns the ICT patents and has granted the company exclusive, worldwide rights.

Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in family medicine, 20th in geriatrics, 25th in primary care and 41st in research among the nation's medical schools. It ranks 32nd in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.

Wake Forest University Baptist Medical Center
Medical Center Blvd.
Winston-Salem, NC 27157-1015
United States
http://www1.wfubmc.edu∞
http://www.medilexicon.com/medicalnews.php?newsid=58021∞

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