Genes, Synapses, and Childhood Cognitive Disorders
Gavin Rumbaugh, The Scripps Research Institute
Developmental brain disorders, such as autism spectrum disorder, intellectual disabilities and epilepsy, are very common, with a combined incidence of nearly 1 in 30 live births worldwide. Most of these patients have cognitive disruptions (e.g. problems think- ing, reasoning, learning, remembering, etc), yet there are no effective therapeutic options available to improve these essential skills, particularly in low-functioning patients with the most severe disorders. One reason for the lack of effective treatments is that the dis- ease mechanisms underlying reduced cognitive ability and behavioral problems are poorly understood. Recent advances in genomic sequencing technology have enabled the large-scale screening of patient DNA. From these studies, it is now clear that random, non- inherited mutations in certain “high-risk” genes cause a substantial portion of childhood brain disorders. Surprisingly, many of these genetic risk factors code for proteins that either directly or indirectly regulate synapses, which are the connections between neurons that drive brain function. This talk will focus on how certain types of genetic mutations disrupt synapses during critical periods of brain development and how these synaptic disruptions may lead to cognitive and behavioral problems commonly seen in patients. Based on these neurobiological findings, we are now engineering tailor-made therapeutics for particular genetic forms of developmental brain disorders. These new therapeutic strategies are designed to directly target genetic disruptions known to cause these disorders, with the hope that these treatments will prevent neurobiological damage in the developing brain associated with cognitive abnormalities.