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Archive - Apr 22, 2012

Swiftly Spreading Gene Linked to Asian Epidemic of Resistant Staph Aureus

National Institutes of Health (NIH) scientists and their colleagues in China, together with a collaborator at the University of California, San Francisco, have described a rapidly emerging Staphylococcus aureus gene, called sasX, which plays a pivotal role in establishing methicillin-resistant S. aureus (MRSA) epidemics in most of Asia. Senior author Michael Otto, Ph.D., of NIH's National Institute of Allergy and Infectious Diseases, says these findings illustrate at the molecular level how MRSA epidemics may emerge and spread. Moreover, the study identifies a potential target for novel therapeutics. MRSA is a leading cause of severe infections that occur predominantly in hospitals. The results were published online in Nature Medicine on April 22, 2012. MRSA epidemics happen in waves, with old clones of MRSA bacteria disappearing and new clones emerging, a process whose molecular underpinnings are not fully understood. Previous data indicated that the sasX gene is extremely rare. Therefore, the researchers were surprised when they analyzed 807 patient samples of invasive S. aureus taken over the past decade from three Chinese hospitals. Their data showed that sasX is more prevalent in MRSA strains from China than previously thought, and the gene's frequency is increasing significantly: From 2003 to 2011, the percentage of MRSA samples containing sasX almost doubled, from 21 to 39 percent. This finding suggests that the sasX gene is involved in molecular processes that help MRSA spread and cause disease. The researchers determined in laboratory and mouse studies that sasX helps bacteria to colonize in the nose, cause skin abscesses and lung disease, and evade human immune defenses.

Fragile X Syndrome Can Be Substantially Reversed in Adult Mouse Brain

A recent study finds that a new compound reverses many of the major symptoms associated with Fragile X syndrome (FXS), the most common form of inherited intellectual disability and a leading cause of autism. The paper, published by Cell Press in the April 12 issue of the journal Neuron, describes the exciting observation that the FXS correction can occur in adult mice, after the symptoms of the condition have already been established. Fragile X patients suffer from a complex set of neuropsychiatric symptoms of varying severity which include anxiety, hyperactivity, learning and memory deficits, low IQ, social and communication deficits, and seizures. Previous research has suggested that inhibition of mGlu5, a subtype of receptor for the excitatory neurotransmitter glutamate, may be useful for ameliorating many of the major symptoms of the disease. The new study, a collaboration between a group at F. Hoffmann-La Roche Ltd. in Switzerland, led by Dr. Lothar Lindemann, and a group at the Picower Institute for Learning at the Massachusetts Institute of Technology, led by Dr. Mark Bear, used a newly developed mGlu5 inhibitor called CTEP to examine whether pharmacologic inhibition of mGlu5 could reverse FXS symptoms. The researchers used a mouse model of FXS and administered CTEP after the brain had matured. "We found that even when treatment with CTEP was started in adult mice, it reduced a wide range of FXS symptoms, including learning and memory deficits and auditory hypersensitivity, as well as morphological changes and signaling abnormalities characteristic of the disease," reports Dr. Lindemann. Although the CTEP drug itself is not being developed for humans, the findings have significance for human FXS.

Early Treatment Improves Outcome in Mysterious Form of Encephalitis

A mysterious, difficult-to-diagnose, and potentially deadly disease that was only recently discovered can be controlled most effectively if treatment is started within the first month that symptoms occur, according to a new report by researchers from the Perelman School of Medicine at the University of Pennsylvania. The researchers analyzed 565 cases of this recently discovered paraneoplastic condition, called anti-NMDA receptor encephalitis, and determined that if initial treatments fail, second-line therapy significantly improves outcomes compared with repeating treatments or no additional treatments (76 percent versus 55 percent). The research will be presented on April 25, 2012 at the American Academy of Neurology's 64th Annual Meeting in New Orleans. The condition occurs most frequently in women (81 percent of cases), and predominantly in younger people (36 percent of cases occurring in people under 18 years of age, the average age is 19). Symptoms range from psychiatric symptoms, memory issues, speech disorders, seizures, involuntary movements, to decreased levels of consciousness and breathing. Within the first month, movement disorders were more frequent in children, while memory problems and decreased breathing predominated in adults. "Our study establishes the first treatment guidelines for NMDA-receptor encephalitis, based on data from a large group of patients, experience using different types of treatment, and extensive long-term follow-up," said lead author Maarten Titulaer, M.D., Ph.D., clinical research fellow in Neuro-oncology and Immunology in the Perelman School of Medicine at the University of Pennsylvania.