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Cincinnati and Boston Children's Hospitals receive an NIH Autism Center of Excellence Grant

A network of five leading medical centers, led by Cincinnati Children's Hospital Medical Center and Boston Children's Hospital, has received a five-year, $12.5 million National Institutes of Health (NIH) grant to learn more about how autism develops.

The five centers, which also include the University of Alabama at Birmingham, Mattel Children's Hospital at UCLA (Los Angeles) and University of Texas Medical School at Houston, will study infants with tuberous sclerosis complex (TSC), a rare genetic disease that causes autism in about 50 percent of cases.

TSC is marked by tumors in the brain and other vital organs and can be diagnosed even before birth, making it possible to observe how the brain's circuitry develops before autism becomes apparent. Through the newly formed TSC Autism Center of Excellence Research Network (TACERN), and in close collaboration with the national Tuberous Sclerosis Alliance, researchers will track infants diagnosed with TSC using advanced brain imaging techniques.

Previous pre-clinical research and human imaging studies led by Boston Children's Hospital neurologist Mustafa Sahin, MD, PhD, has identified defects in axons (nerve fibers) and their orientation into nerve tracts in TSC, particularly in TSC patients that develop autism, supporting the growing idea that autism results from a miswiring of connections in the developing brain. Sahin's lab has also shown that the defects arise from a biological pathway that can be reversed using the drug rapamycin. A clinical trial of a related drug, everolimus, is now ongoing at Boston Children's and Cincinnati Children's, with the goal of improving cognition and behavior.

Clinical research conducted by physicians at Cincinnati Children's has resulted in the first FDA-approved medical therapy for TSC. This research demonstrated that everolimus, originally developed to prevent the rejection of transplanted organs, dramatically reduces a particular kind of brain tumor in patients with TSC, as well as non-cancerous kidney tumors that affect up to 80 percent of people with TSC. The Cincinnati research team also discovered that brain connectivity, as indicated by a cutting-edge imaging technique known as diffusion tensor imaging (DTI), improved with everolimus treatment.

Building on the prior studies from Boston and Cincinnati, the TACERN study will investigate whether DTI can be used a marker to identify TSC patients at highest risk for autism during early development, providing a window for intervention in future trials.

"The new study is unique in that we are focused on a specific disorder with high rates of autism for which the molecular cause is already known and molecular-targeted treatments are already available," says Darcy Krueger, MD, PhD, a pediatric neurologist and director of research in the division of Neurology at Cincinnati Children's. "Our study will open new avenues of research and treatment for autism, not only in TSC but in other causes as well."

The DTI studies will be led by Simon Warfield, PhD, of the Computational Research Laboratory at Boston Children's Hospital. Brain wiring will also be analyzed with EEG techniques, and the infants will undergo frequent neuropsychological assessments from 3 months to 3 years of age, when a clinical diagnosis of autism can be made.

"Our ultimate goal is to identify which tuberous sclerosis patients are at high risk for autism so we can intervene early," says Sahin. "This may have implications for autism in patients without tuberous sclerosis as well."

The grant was one of nine awarded by the National Institutes of Health for its Autism Centers of Excellence research program. The NIH created the program in 2007 "to launch an intense and coordinated research program into the causes of autism spectrum disorders and to find new treatments." The nine grants totaled more than $100 million.

Contact: Jim Feuer
Cincinnati Children's Hospital Medical Center

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