Posted on 02/07/2010 1:19:50 PM PST by decimon
Finding, in animal model, offers proof of principle that inhibiting serotonin in the gut could become a novel treatment for 10s of millions of osteoporosis sufferers
NEW YORK – An investigational drug that inhibits serotonin synthesis in the gut, administered orally once daily, effectively cured osteoporosis in mice and rats reports an international team led by researchers from Columbia University Medical Center, in the Feb. 7 issue of Nature Medicine. Serotonin in the gut has been shown in recent research to stall bone formation. The finding could lead to new therapies that build new bone; most current drugs for osteoporosis can only prevent the breakdown of old bone.
"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 Gerard Karsenty, M.D., Ph.D., chair of the Department of Genetics and Development at Columbia University College of Physicians and Surgeons, lead author of the paper. "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 Nature Medicine paper follows on a major discovery: http://www.cumc.columbia.edu/news/press_releases/Karsenty-cell-serotonin-lrp5.html, also made by Dr. Gerard Karsenty's group (published in the Nov. 26, 2008 issue of Cell), 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 this 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 five 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 this new study, to cure osteoporosis in mice that had undergone menopause.
Based on their findings reported in the Cell paper, Dr. Karsenty and his team postulated that an inhibitor of serotonin synthesis should be an effective treatment for osteoporosis. Shortly thereafter, they read about an investigational drug, known as LP533401, which is able to inhibit serotonin in the gut. "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 Dr. Karsenty.
Dr. Karsenty and his team developed a research protocol to test their theory, where they administered the compound orally, once daily, at a small dose, for up to six weeks to rodents experiencing post-menopausal osteoporosis. 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 compound did not enter the general circulation and was unable to cross the blood-brain barrier, thereby avoiding many potential side effects.
Implications for the Treatment of Osteoporosis:
Most osteoporosis drugs, including those currently under clinical investigation, do not generate new bone but rather, prevent the breakdown of old bone. Only one drug currently on the market can generate new bone – but it must be taken by injection once a day, and because it may increase the risk of bone cancer, at least in rats, its use is restricted for short-term use in women with severe osteoporosis.
"There is an urgent need to identify new, safe therapies that can increase bone formation on a long term basis and to such an extent that they compensate for the increase in bone resorption caused by menopause," said Dr. Karsenty. "Furthermore, it is important to note that since this study was conducted in rodents, it will need further confirmation in human subjects."
Osteoporosis: A Disease of Bone Mass Decline…
Osteoporosis is a growing public health concern, with the aging population and the incidence of post-menopausal osteoporosis on the rise. It is a disease of low bone mass, most often caused by an increase in bone resorption not compensated by a similar increase in bone formation.
Far from being inert, bone constantly undergoes renovation, with some cells responsible for removing old material and other cells responsible for creating new bone. In humans, after age 20, the balance between bone formation and breakdown tips toward breakdown, and bone mass starts to decline. In women, the rate of decline increases after menopause, when estrogen levels drop and cells that tear down old bone become overactive. Osteoporosis is a disease in which bones become fragile and porous, increasing the risk of breaks. It is diagnosed when bone mass drops below a certain level.
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This research was supported by grants from the National Institutes of Health and a Gideon and Sevgi Rodan fellowship from the International Bone and Mineral Society (IBMS).
Co-authors on this paper include Vijay K. Yadav from the Department of Genetics and Development at Columbia University Medical Center (CUMC); Santhanam Balaji and Marc Vidal, Department of Genetics, Harvard Medical School; P.S. Suresh and R. Medhamurthy, Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, India; X. Sherry Liu, Xin Lu and Edward Guo, Department of Biomedical Engineering (Columbia); Zhishan Li and Michael D. Gershon, Department of Cell Biology (CUMC); J. John Mann, Department of Psychiatry (CUMC); Anil K. Balapure, Tissue and Cell Culture Unit, Central Drug Research Institute, India; and Patricia Ducy, Department of Pathology (CUMC).
Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future health care leaders at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians & Surgeons was the first in the country to grant the M.D. degree. Columbia University Medical Center is home to the largest medical research enterprise in New York City and state and one of the largest in the United States. Visit www.cumc.columbia.edu.
Gut feelings ping.
I would imagine this could be applied MANY other disorders.
Great news, I fear drugs like Boniva, the contraindications are numerous and the drug really does not create needed new bone. I take a special form of calcium I buy to avoid these drugs, this could be wonderful news for those of us who suffer with this disease.
I figured there would be a few here.
I buy it from Tango Advanced Nutrition online. I believe it is made from oyster shells, I also take their Vital Cell and Herbal Boost. So far I feel great and don’t have all the Boniva side effects. Check them out, they are an interesting company with some good herbal medications that many folks swear by.
I will thanks!
I suppose you are also aware of the importance of weight-bearing exercise.
The oral drug, known as LP533401, was developed for the treatment of irritable bowel syndrome (IBS) and it has been tested in humans at high doses, he says.
Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis link to abstract
Nature Medicine had this comment on its advance online publication page:
Osteoporosis results from misregulation of bone catabolism and bone anabolism, resulting in severe bone loss. Most current therapies act by decreasing bone catabolism, but targeting bone anabolism is more desired, because once bone is lost, it is difficult to replace. In a new report by Gerard Karsenty and his colleagues, they show that orally delivered pharmacological targeting of serotonin synthesis in the gut is sufficient to increase bone anabolism and thus restore lost bone in rat and mouse models of well-established osteoporosis.
This looks like a good one. I of course would like to know if any natural substances inhibit intestinal serotonin production.
There’s another thread about beer, or some beer, helping with osteoporosis and apparently because of contained silicon. It doesn’t say what the silicon does.
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