Very exciting new research on treating osteoporosis! So far in animal studies but moving to clinical trials for IBS and hopefully soon osteoporosis. This is particularly interesting in light of the recent retrovirual conference in SF in which animal studies showed XMRV in the gut. Maybe XMRV in the gut causes excess serotonin and that reduces bone density!!! The puzzle pieces just might come together. ~Fern
Gut-derived serotonin inhibition offers novel osteoporosis strategy
By Lynda Williams
10 February 2010
Nature Med 2010; Advance online publication
MedWire News: Gut-derived serotonin (GDS) production may offer a novel target for anti-osteoporosis therapies, suggests preliminary research published in the journal Nature Medicine.
“These results provide a proof of principle that inhibiting GDS biosynthesis could become a new anabolic treatment for osteoporosis,” say Gerard Karsenty (Columbia University Medical Center, New York, USA) and co-authors.
The majority of serotonin is located in the duodenum and, as reported by MedWire News, the team demonstrated previously that gut serotonin inhibits bone mass accrual.
The researchers now say that blocking GDS production prevented and reversed osteoporosis in postmenopausal mice, without altering serotonin levels in the brain.
To investigate, the team synthesized a small molecular inhibitor of tryptophan hydroxylase-1 (Tph-1), the first enzyme required for biosynthesis of GDS. The small molecule, LP533401, or a placebo was fed to ovariectomized mice and controls for 28 days at varying doses.
As expected, ovariectomized mice given placebo developed osteopenia, while sham-surgery mice did not. However, ovariectomized mice given LP533401 had higher bone mass than placebo-treated mice, and this was attributed to an increase in osteoblast numbers, the bone formation rate, and osteocalcin serum levels.
“These results establish that LP533401 can prevent the development of ovariectomy-induced osteoporosis in mice,” the team reports.
Next, the researchers examined the impact of GDS inhibition on ovariectomized mice left untreated for 6 weeks before a 6-week course of LP533401 or placebo. Importantly, LP533401 treatment reversed ovariectomy-induced osteopenia in the vertebrae and long bones of the mice, increasing bone mass comparable to levels found in sham-surgery animals.
“These results establish that LP533401 can rescue, through a bone anabolic mechanism, ovariectomy-induced osteoporosis in mice even when given at a low dose (25 mg/kg body weight per day) and late after ovariectomy and that it does so without deleterious consequences on hsemostasis or intestinal motility,” say the authors.
While the impact of LP533401 has yet to be investigated in humans, the researchers conclude: “ The fact that this small molecule can be administered orally, promotes only bone formation and, for the purpose of treating osteoporosis, is needed at a relatively small dose and only once daily, suggests that inhibitors of GDS synthesis have the potential to become a new class of bone anabolic drugs that can be added to the armamentarium to treat osteoporosis.”
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www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. Springer Healthcare Ltd; 2010
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