Inhibiting Serotonin Cures Osteoporosis in Animal Model

A recent animal study showed that it may be possible to delay or cure osteoporosis with a drug that inhibits the production of serotonin in the gut.

Osteoporosis is a disease of low bone mass most often caused by an increase in bone resorption that is not sufficiently compensated by a corresponding increase in bone formation. Investigators at Columbia University (New York, NY, USA) had shown in earlier studies that 95% of the body's serotonin is found in the gut, where its major function is to inhibit bone formation. In the current study, they sought to learn what would happen to bone metabolism if the action of serotonin could be neutralized.

To this end, they treated mice and that had their ovaries removed to mimic human menopause with the drug LP533401. This drug is a small molecule inhibitor of tryptophan hydroxylase-1 (Tph-1), the initial enzyme in gut derived serotonin biosynthesis. The animals received the drug orally once daily for up to six weeks.
Results published in the February 7, 2010, online edition of the journal Nature Medicine revealed that this drug regimen prevented osteoporosis from developing or cured the disease if it were already present. Importantly, the drug did not lower levels of serotonin in the brain.

"When we learned of this compound, we thought that it was important to test it as proof of principle that there could be novel ways to treat osteoporosis with therapies that can be taken orally and regulate the formation of serotonin," said contributing author Dr. Gerard Karsenty, professor of genetics at Columbia University.

"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. Karsenty. "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."

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