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Serotonin Inhibitor Appears to Cure Osteoporosis in Rodents

An investigational drug that inhibits serotonin synthesis in the gut effectively cured osteoporosis in mice and rats when administered orally once a day, according to a report by an international team led by researchers from the Columbia University Medical Center. "New therapies that inhibit the production of serotonin in the gut have the potential to become a novel class of drugs to be added to the therapeutic arsenal against osteoporosis," said Dr. Gerard Karsenty, Chair of the Department of Genetics and Development at the Columbia University College of Physicians and Surgeons, and a senior author of the report. "With tens of millions of people worldwide affected by this devastating and debilitating bone loss, there is an urgent need for new treatments that not only stop bone loss, but also build new bone. Using these findings, we are working hard to develop this type of treatment for human patients." The current study followed up on an earlier report, in Cell (November 28, 2008), by Dr Karsenty’s group and colleagues, showing that serotonin released by the gut inhibits bone formation, and that regulating the production of serotonin within the gut affects the formation of bone. Prior to that discovery, serotonin was primarily known as a neurotransmitter acting in the brain. Yet, 95 percent of the body's serotonin is found in the gut, where its major function is to inhibit bone formation (the remaining 5 percent is in the brain, where it regulates mood, among other critical functions). By turning off the intestine's release of serotonin, the team was able, in the new study, to cure osteoporosis in rodents that had undergone menopause. The results demonstrated that osteoporosis was prevented from developing, or when already present, could be fully cured. Of critical importance, levels of serotonin were normal in the brain, which indicated that the investigational compound did not enter the general circulation and was unable to cross the blood-brain barrier, thereby avoiding many potential side effects. "It is important to note that since this study was conducted in rodents, it will need further confirmation in human subjects," Dr. Karsenty cautioned. The new results were published online in the February 7 issue of Nature Medicine. [Press release 2010] [Press release 2008] [Cell abstract 2008] [Nature Medicine abstract 2010]