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Archive - Feb 10, 2013

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NIH Scientists Discover Promising Target to Block Staphylococcus Infection

NIH scientists have identified a promising lead for developing a new type of drug to treat infection caused byStaphylococcus aureus, a bacterium that frequently resists traditional antibiotics. The researchers discovered a system used by S. aureus to transport toxins that are thought to contribute to severe staph infections. These toxins—called phenol-soluble modulins (PSMs)—have gained much attention in recent years, but their multitude and diversity have hindered efforts to target them for drug development. Expanding on work that first described S. aureus PSMs in 2007, scientists at the NIH's National Institute of Allergy and Infectious Diseases found that the transport system, which they call Pmt, is common to all S. aureus PSMs and critical for bacterial proliferation and disease development in a mouse model. Their experiments suggest that a drug interfering with Pmt's function could not only prevent production of the PSM toxins, but also lead directly to bacterial death. Although their study focused on S. aureus, the scientists suspect that Pmt performs the same role in other staphylococci, such as S. epidermidis, the leading cause of hospital-associated infections involving in-dwelling medical devices such as catheters, pacemakers, and prosthetics. They plan to continue their studies to improve the understanding of how PSMs function and to learn how to interfere with the Pmt transport system to block disease. The report was published online on February 10, 2013 in Nature Medicine. [Press release] [Nature Medicine abstract]

24 New Genes for Short-Sightedness Identified

An international team of scientists led by a group at King's College London has discovered 24 new genes that cause refractive errors and myopia (short-sightedness). Myopia is a major cause of blindness and visual impairment worldwide, and currently there is no cure. These findings, published online on February 10, 2013 in Nature Genetics, reveal genetic causes of the trait, which could lead to finding better treatments or ways of preventing the condition in the future. Thirty per cent of Western populations and up to 80 per cent of Asian people suffer from myopia. During visual development in childhood and adolescence the eye grows in length, but in myopes it grows too long, and light entering the eye is then focused in front of the retina rather than on it. This results in a blurred image. This refractive error can be corrected with glasses, contact lenses or surgery. However, the eye remains longer, the retina is thinner, and this may lead to retinal detachment, glaucoma, or macular degeneration, especially with higher degrees of myopia. Myopia is highly heritable, although up to now, little was known about the genetic background. To find the genes responsible, researchers from Europe, Asia, Australia, and the United States collaborated as the Consortium for Refraction and Myopia (CREAM). They analyzed genetic and refractive error data for over 45,000 people from 32 different studies, and found 24 new genes for this trait, and confirmed two previously reported genes. Interestingly, the genes did not show significant differences between the European and Asian groups, despite the higher prevelance among Asian people. The new genes include those which function in brain and eye tissue signalling, the structure of the eye, and eye development.

Old Drug May Lead to New Treatments for Diabetes and Obesity

Researchers at the University of Michigan's (U-M) Life Sciences Institute have found that amlexanox, an off-patent drug currently prescribed for the treatment of asthma and other uses, also reverses obesity, diabetes, and fatty liver in mice. The findings from the lab of Dr. Alan Saltiel, the Mary Sue Coleman director of the Life Sciences Institute, were published online on February 10, 2013 in Nature Medicine. "One of the reasons that diets are so ineffective in producing weight loss for some people is that their bodies adjust to the reduced calories by also reducing their metabolism, so that they are 'defending' their body weight," Dr. Saltiel said. "Amlexanox seems to tweak the metabolic response to excessive calorie storage in mice." Different formulations of amlexanox are currently prescribed to treat asthma in Japan and canker sores in the United States. Dr. Saltiel is teaming up with clinical trial specialists at U-M to test whether amlexanox will be useful for treating obesity and diabetes in humans. He is also working with medicinal chemists at U-M to develop a new compound based on the drug that optimizes its formula. The study appears to confirm and extend the notion that the genes IKKE and TBK1 play a crucial role for maintaining metabolic balance, a discovery published by the Saltiel lab in 2009 in the journal Cell. "Amlexanox appears to work in mice by inhibiting two genes—IKKE and TBK1—that we think together act as a sort of brake on metabolism," Dr. Saltiel said. "By releasing the brake, amlexanox seems to free the metabolic system to burn more, and possibly store less, energy." Using high-throughput chemical screening at LSI's Center for Chemical Genomics to search for compounds that inhibit IKKE and TBK1, the researchers hit upon an approved off-patent drug: amlexanox.