Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Inhibiting serotonin in gut could cure osteoporosis

08.02.2010
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

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.

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.

Elizabeth Streich | EurekAlert!
Further information:
http://www.columbia.edu
http://www.cumc.columbia.edu

More articles from Health and Medicine:

nachricht New way to target advanced breast cancers
24.09.2018 | Jackson Laboratory

nachricht Neutrons produce first direct 3D maps of water during cell membrane fusion
21.09.2018 | DOE/Oak Ridge National Laboratory

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Hygiene at your fingertips with the new CleanHand Network

The Fraunhofer FEP has been involved in developing processes and equipment for cleaning, sterilization, and surface modification for decades. The CleanHand Network for development of systems and technologies to clean surfaces, materials, and objects was established in May 2018 to bundle the expertise of many partnering organizations. As a partner in the CleanHand Network, Fraunhofer FEP will present the Network and current research topics of the Institute in the field of hygiene and cleaning at the parts2clean trade fair, October 23-25, 2018 in Stuttgart, at the booth of the Fraunhofer Cleaning Technology Alliance (Hall 5, Booth C31).

Test reports and studies on the cleanliness of European motorway rest areas, hotel beds, and outdoor pools increasingly appear in the press, especially during...

Im Focus: Scientists present new observations to understand the phase transition in quantum chromodynamics

The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.

This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.

Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...

Im Focus: Patented nanostructure for solar cells: Rough optics, smooth surface

Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.

"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...

Im Focus: New soft coral species discovered in Panama

A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.

Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...

Im Focus: New devices based on rust could reduce excess heat in computers

Physicists explore long-distance information transmission in antiferromagnetic iron oxide

Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

"Boston calling": TU Berlin and the Weizenbaum Institute organize a conference in USA

21.09.2018 | Event News

One of the world’s most prominent strategic forums for global health held in Berlin in October 2018

03.09.2018 | Event News

4th Intelligent Materials - European Symposium on Intelligent Materials

27.08.2018 | Event News

 
Latest News

Small modulator for big data

25.09.2018 | Information Technology

NASA's Terra Satellite glares at the 37-mile wide eye of Super Typhoon Trami

25.09.2018 | Earth Sciences

Rice U. study sheds light on -- and through -- 2D materials

25.09.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>