A gene construct that reacts to blue light could offer a drug-free remedy for men with erectile dysfunction. Researchers at ETH Zurich’s Department of Biosystems in Basel have tested the construct, which they call an erectile optogenetic stimulator (EROS), in male rats. They found that it could be used to reliably “turn on” erections and in some cases cause ejaculation. When the construct is exposed to the light, a precursor molecule (guanosine triphosphate, or GTP) is converted into the second messenger cyclic guanosine monophosphate (cGMP), which exists naturally in a number of human organs. This allows voltage-dependent calcium channels to close, thereby reducing calcium levels in the cells, which in turn relaxes muscle cells and increases blood flow to erectile tissue. An enzyme then slowly breaks down cGMP so that the erection wears off with time. A male rat is exposed to blue light after injection with a light-activated gene construct that triggers erections. Courtesy of Martin Fussenegger/ETH Zurich. “Photostimulated short-circuiting of complex psychological, neural, vascular and endocrine factors to stimulate penile erection in the absence of sexual arousal may foster novel advances in the treatment of erectile dysfunction,” the researchers wrote in Angewandte Chemie International Edition (doi: 10.1002/anie.201412204). An estimated 30 million American men are affected by erectile dysfunction, according to the National Institutes of Health. About 4 percent of men in their 50s, 17 percent of men in their 60s and 47 percent of men over 75 experience the condition. Drugs used to treat erectile dysfunction have disadvantages. While they serve to prolong erections, they cannot trigger them. Additionally such drugs cannot be used by people with certain medical conditions including heart disease. Light-based gene therapy, according to the Swiss researchers, may offer a direct route to erection without side-effects. “Injection of a gene construct should not be a barrier to potential users, as injections in the erectile tissue are already a standard treatment for erectile dysfunction these days,” said ETH Zurich professor Dr. Martin Fussenegger. Erectile tissue is largely insensitive to pain; it is also, for the most, part detached from normal blood circulation, so the probability that the gene construct could reach other parts of the body is very low. In addition, cGMP breaks down relatively quickly. Fussenegger said clinical testing would be required before the technique could be used as a treatment for humans. His team is now looking for partners to develop the technology for clinical use. For more information, visit www.ethz.ch.