Randomized Phase 2 Trial of RAD001 (An MTOR Inhibitor) in Patients With Tuberous Sclerosis Complex
Boston Children's Hospital
Autism spectrum disorder (ASD) is a major public health problem that disrupts families and leads to significant disability. There is no treatment aimed at the neurobiological bases of ASD. Tuberous sclerosis complex (TSC) provides an ideal model for autism research, given the very high rates of autism spectrum disorders associated with TSC and its increasingly well-characterized genetic and molecular basis. Breakthrough findings are emerging from studies of both animal models and children with TSC, of which 25-60% have ASD. The undisputed identification of two genes that cause TSC has led to the development of mouse models for TSC, which allows researchers to study the particular deleterious effects of the genetic mutations on brain functioning. There is promising evidence that these genes may cause defects in brain wiring and the connections among brain cells, and that these wiring abnormalities can be prevented or reversed by a class of drugs: the mTOR inhibitors. This Phase II randomized, placebo-controlled trial study will evaluate the efficacy of RAD001, an mTOR inhibitor, in 6-21 year old individuals with TSC, to test the hypothesis that mTOR inhibition may improve aspects of neurocognition in children and young adults with TSC. It will use a broad battery of neurocognitive tests to evaluate the study participants before, during and after treatment. While this trial is limited to individuals with TSC, the mTOR pathway has been implicated in other ASD-associated diseases such as Fragile X and patients with PTEN mutations. Therefore, it is hoped that findings from this study, although limited to individuals with TSC, may have implications for other subpopulations of individuals with ASD in the future.