Study of human brains links gene activity to disorder’s severity, flagging targets for future therapies
Science Daily | May 16, 2019
Scientists have learned in recent years that autism spectrum disorders (ASDs) are typically caused by changes in the genetic instructions for how the developing brain wires itself up, beginning in the second trimester of pregnancy and continuing through early childhood. It is far less clear how the mature brain circuitry produced by those garbled instructions differs in people with autism or how these changes produce the social communication difficulties; restricted, repetitive behaviors; and other symptoms that define the disorder. This is one of the reasons there are currently no medical therapies to reverse or treat these symptoms, say the authors of the new study.
“Identifying genetic changes that occur at conception or in utero is important for understanding the causes of autism, but these insights are unlikely to result in useful therapeutic targets,” said senior author Arnold Kriegstein, MD, PhD, a professor of neurology and member of the UCSF Weill Institute for Neuroscience who directs UCSF’s Eli and Edyth Broad Center for Regeneration Medicine and Stem Cell Research. “By the time children are diagnosed with autism, all of the things that went wrong have happened already, and the patients are left with a circuit dysfunction that has now matured. If we want to be able to offer treatments to these children when they come to our attention, it’s the altered brain circuits that we’re going to have to tackle.”
In the new study — published in the May 17, 2019 issue of Science — researchers led by Dmitry Velmeshev, PhD, a postdoctoral scholar in Kriegstein’s lab, set out to understand how the brains of people diagnosed with autism differ from non-autistic brains at the neural circuit level by using novel techniques to look for differences in gene activity in specific types of brain cells.