Concert Pharmaceuticals, Inc. today announced that it has initiated a Phase 1 clinical trial with CTP-354. CTP-354 is a novel GABAA receptor subtype-selective modulator that has demonstrated no sedation at therapeutic doses in preclinical models in contrast to existing GABAA receptor non-selective agonists, such as benzodiazepines. Concert is developing CTP-354 for the potential treatment of spasticity and chronic pain. The Phase 1 single ascending dose study will evaluate the safety, tolerability and pharmacokinetics of CTP-354 in healthy volunteers. The company also intends to conduct a Positron Emission Tomography (PET) study to assess brain receptor occupancy of CTP-354 in healthy volunteers. Concert expects to report top-line results of the Phase 1 single ascending dose study by year-end.

"Based on CTP-354's preclinical profile, we believe it has the potential to offer patients effective treatment for these chronic conditions with an improved therapeutic profile. We look forward to assessing CTP-354 in our clinical program."

"There is a significant unmet need for effective and better tolerated agents in the treatment of both spasticity and chronic pain, particularly treatments that would reduce or avoid the adverse events of sedation and ataxia that are commonly associated with existing treatments," said Roger Tung, Ph.D., President and Chief Executive Officer of Concert Pharmaceuticals. "Based on CTP-354's preclinical profile, we believe it has the potential to offer patients effective treatment for these chronic conditions with an improved therapeutic profile. We look forward to assessing CTP-354 in our clinical program."

The Phase 1 study is a randomized, double-blind, placebo controlled study to assess single ascending doses of CTP-354 in healthy adult volunteers in the United States. The program advanced into Phase 1 clinical testing following successful preclinical studies with CTP-354 (previously referred to as C-21191). CTP-354 was developed based on an earlier generation of investigational GABAA receptor modulators that demonstrated promising receptor subtype selectivity, but lacked a favorable pharmacokinetic profile. Concert's selective incorporation of deuterium in CTP-354 significantly improved pharmacokinetic properties in preclinical models while maintaining the desirable pharmacological activity seen with the earlier generation modulators.

SOURCE Concert Pharmaceuticals Inc.

A new study has found that one in four men seeking medical help for newly-developed erectile dysfunction (ED) was younger than 40 years, and nearly half of young men with the condition had severe ED.

While larger population-based studies are needed, the findings suggest that erectile dysfunction in young men may be more prevalent and more serious than previously thought.

Erectile dysfunction is a common complaint in men over 40 years of age.

Prevalence increases with age, but the prevalence and risk factors of erectile dysfunction among younger men have been scantly analyzed.

The research that has been done paints a vague picture, reporting prevalence rates ranging between two percent and nearly 40 percent.

To provide more clarity, Paolo Capogrosso, MD, of the University Vita-Salute San Raffaele, in Milan, Italy, and his colleagues assessed the sociodemographic and clinical characteristics of 439 men seeking medical help for newly-developed erectile dysfunction between January 2010 and June 2012 at a single academic outpatient clinic.

Of the 439 patients, 114 (26 percent) were aged 40 years or younger.

Compared with older patients, younger patients had a lower average body mass index, a higher average level of testosterone in the blood, and a lower rate of other medical conditions. (Only 9.6 percent of younger patients had one or more concomitant medical conditions compared with 41.7 percent among older patients.)

Younger ED patients smoked cigarettes and used illicit drugs more frequently than older patients.

Premature ejaculation was more common in younger men, whereas Peyronie`s disease (bent erection from scar tissue) was more prevalent in older patients.

Severe erectile dysfunction was found in 48.8 percent of younger patients and 40 percent of older patients while the rates of mild, mild-to-moderate, and moderate erectile dysfunction were not significantly different between the two groups.

The findings are published in The Journal of Sexual Medicine.

Scientists have discovered a mechanism that guides the exquisite wiring of neural circuits in a developing brain-gaining unprecedented insight into the faulty circuits that may lead to brain disorders ranging from autism to mental retardation.

The researchers at Weill Cornell Medical College explained that faulty wiring occurs when RNA molecules embedded in a growing axon are not degraded after they give instructions that help steer the nerve cell. So, for example, the signal that tells the axon to turn-which should disappear after the turn is made-remains active, interfering with new signals meant to guide the axon in other directions.

The scientists said that there might be a way to use this new knowledge to fix the circuits.

"Understanding the basis of brain miswiring can help scientists come up with new therapies and strategies to correct the problem," said the study`s senior author, Dr. Samie Jaffrey, a professor in the Department of Pharmacology.

"The brain is quite `plastic` and changeable in the very young, and if we know why circuits are miswired, it may be possible to correct those pathways, allowing the brain to build new, functional wiring," he said.

Disorders associated with faulty neuronal circuits include epilepsy, autism, schizophrenia, mental retardation and spasticity and movement disorders, among others.

In this study, researchers investigated neurons that travel up the spinal cord into the brain.

"It is very critical that axons are precisely positioned in the spinal cord. If they are improperly positioned, they will form the wrong connections, which can lead to signals being sent to the wrong target cells in the brain," Dr. Jaffrey said.

The team found that RNA molecules embedded in the growth cone are responsible for instructing the axon to move left or right, up or down. These RNAs are translated in growth cones to produce antenna-like proteins that steer the axon like a self-guided missile.

"As a circuit is being built, RNAs in the neuron`s growth cones are mostly silent. We found that specific RNAs are only read at precise stages in order to produce the right protein needed to steer the axon at the right time. After the protein is produced, we saw that the RNA instruction is degraded and disappears," he said.

"If these RNAs do not disappear when they should, the axon does not position itself properly-it may go right instead of left-and the wiring will be incorrect and the circuit may be faulty," Dr. Jaffrey explained.

The research finding answers a long-standing puzzle in the quest to understand brain wiring, added Dr. Dilek Colak, a postdoctoral associate in Dr. Jaffrey`s laboratory.

The study was published in the journal Cell.

People need to talk about excessive use of antibiotics without getting emotional or mixing politics into the discussion, Ada Yonath, who won the 2009 Nobel Prize in Chemistry, said.

"Perhaps we committed errors in using antibiotics for treating viral diseases ... but we learned that that does not work. We learned a bunch of things ... so it is incorrect to say we are abusing antibiotics," Yonath said.

Yonath is one of the scientists participating in the 3rd World Summit on Evolution on Ecuador`s Galapagos Islands.

The summit, which ends Thursday, is taking place in Puerto Baquerizo Moreno, where leading scientists are discussing evolution, genomics, microorganisms and diseases, among other topics.

Yonath said antibiotics were extremely useful, but she criticized the "political" use of the issue.

The use of antibiotics to fight bacterial infections has allowed average life expectancies to rise from 40 or 50 years to double that in just a few decades, Yonath said.

Vegetarian diets have been linked with reductions in risk for several chronic diseases, including hypertension, but a new study has claimed that they are also associated with reduced death rates.

Michael J. Orlich, M.D., of Loma Linda University in California, and colleagues examined all-cause and cause-specific mortality in a group of 73,308 men and women Seventh-day Adventists.

Researchers assessed dietary patients using a questionnaire that categorized study participants into five groups: non-vegetarian, semi-vegetarian, pesco-vegetarian (includes seafood), lacto-ovo-vegetarian (includes dairy and egg products) and vegan.

The study noted that some evidence suggested that vegetarian dietary patterns could be associated with reduced mortality, but the relationship is not well established.

There were 2,570 deaths among the study participants during a mean (average) follow-up time of almost six years.

The overall mortality rate was six deaths per 1,000 person years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs. non-vegetarians was 0.88, or 12 percent lower, the study results showed.

The association also appears to be better for men with significant reduction in cardiovascular disease mortality and IHD death in vegetarians vs. non-vegetarians. In women, there were no significant reductions in these categories of mortality, the results indicate.

The authors wrote that the results demonstrate an overall association of vegetarian dietary patterns with lower mortality compared with the non-vegetarian dietary pattern.

The findings have been published online by JAMA Internal Medicine.