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Archive - Feb 2010

Date

February 7th

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.

February 5th

HPV Vaccines May Reduce Wide Range of Genital Diseases

High-coverage human papillomavirus (HPV) vaccinations among adolescent and young women may result in a rapid reduction of genital warts, cervical cell abnormalities, and diagnostic and therapeutic procedures, researchers report in a new study published online February 5 in the Journal of the National Cancer Institute. Some of these genital abnormalities are precursors of cervical, vulvar, and vaginal cancers. The study focused on 17,622 women enrolled in one of two randomized, placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine. All women underwent cervicovaginal sampling and Pap testing. In the group representing uninfected women, vaccination was up to 100% effective in reducing the risk of HPV16/18-related high-grade cervical, vulvar, and vaginal lesions and in reducing the risk of HPV6/11-related genital warts. In the group representing the general population, vaccination reduced the risk of any lesion, genital warts, Pap abnormalities, and definitive therapy, irrespective of HPV type. The reduction in risk was statistically significant. "Our results provide strong evidence to suggest that the ongoing HPV vaccination programs in adolescent girls and young women will result within a few years in a notable reduction of genital warts, cervical cytological abnormalities, and diagnostic and therapeutic procedures related to precursor lesions in the cervix, vulva, and vagina," the authors wrote. "It is anticipated that these reductions will eventually translate into lower rates of cancer of the cervix, vulva, and vagina." [Press release] [JNCI abstract]

Artificial Pancreas System Shows Promise in Type 1 Diabetes

In a study in children and teenagers with type 1 diabetes, researchers have shown that using a first-generation artificial pancreas system overnight can lower the risk of low blood sugar emergencies while sleeping, and at the same time improve diabetes control. The closed-loop system combined commercially available blood glucose sensors and insulin pumps, controlled by a sophisticated computer program that determined insulin dosage based on blood glucose levels while participants slept. Maintaining recommended blood sugar levels overnight is a major issue for people with type 1 diabetes--and particularly for the families of children with diabetes--because of the possibility of blood glucose dropping dangerously low during sleep and going unnoticed, which can lead to seizures, coma, and in some cases be fatal. Notably, the study showed that the children and teenagers spent twice as much time during the night within targeted blood glucose levels when their diabetes was regulated with the artificial pancreas system than when they followed conventional "manual" therapy—and low blood sugars were minimized. "Without a doubt, the biggest worry for parents of kids with type 1 diabetes is that their child will have a low blood sugar emergency during the night, when they're hard to identify," said Dr. Aaron Kowalski, Assistant Vice President of Metabolic Control at the Juvenile Diabetes Research Foundation (JDRF) and Director of the JDRF Artificial Pancreas Project. "This study is proof of principle that diabetes in kids can be safely managed overnight with an artificial pancreas.

February 4th

Potential New Class of AIDS Drugs Identified

Two compounds that act on novel binding sites for HIV protease--an enzyme critical to the life cycle of the virus that causes AIDS--have been identified by researchers at the Scripps Research Institute and collaborating institutions, including Pfizer and GlaxoSmithKline. The discovery lays the foundation for the development of a new class of anti-HIV drugs to enhance existing therapies, treat drug-resistant strains of the disease, and slow the evolution of drug resistance in the virus. Drugs that block the HIV protease already exist and currently make up an important part of the successful AIDS drug cocktail known as highly active anti-retroviral therapy (HAART). Compared with the nine U.S. Food and Drug Administration (FDA)-approved drugs that target HIV protease, however, the two new compounds, which are small chemical units or "fragments," bind with two novel parts of the molecule. This could make future drugs incorporating the fragments' novel structural elements a useful complement to existing treatments. "The study's results open the door to a whole new approach to drug design against HIV protease," said Scripps Research Associate Professor C. David Stout, senior author of the study. "The fragments bound at not one, but two, different crevices in protease outside the active site. This is an important proof-of-concept that the protease molecule has two non-active site binding pockets (allosteric sites) which can now be exploited as a powerful new strategy to combat drug-resistance in HIV." The article describing this work is currently available online and will be featured as the cover story of the March issue of Chemical Biology & Drug Design. [Press release]