Decoding Autism

Eric Morrow, MD, PhD, wears many hats. As a psychiatrist, he works with patients and families at Bradley Hospital, a partner of the Warren Alpert Medical School. As a molecular neuroscientist and geneticist in the Department of Molecular and Cellular Biology and Biochemistry at Brown, he uses molecular methods, particularly genetics, to understand conditions like autism and related neuropsychiatric conditions. When Morrow began his work in the field, these conditions were among "the most enigmatic in all of medicine," he says. "They affect childhood brain development—and families—in profound ways."

The mighty genome

In recent years, good news has emerged for patients and families—much of it due to the advent of genome sequencing. "What I've seen in the 15 years I've been doing this, I would never have imagined," Morrow says. "We now have thousands and thousands of genomes that have been sequenced, so we can understand how, for example, the genome in some children with autism is different—how the DNA has changed in an autistic child as compared to typically developing siblings." By assembling a genome directory, scientists have created a map that shows what change in a child's DNA contributed to the disorder.

One of Morrow's current efforts is to implement more genetic testing in the clinical setting. This is known as precision medicine, and it is leading to new standards of care. "A child with a new diagnosis of autism or developmental disability can now get a genetic test or genomic sequence," says Morrow. "That's really amazing."

The discovery of genetic changes in autism is a powerful tool for scientists because it provides a way to explore a complex problem. "We are able to sequence the genome of children with a new diagnosis of a developmental disorder and, 10 to 20 percent of the time, come up with a genetic diagnosis that is a medical explanation," Morrow says. "And by following the genetic mutations in the lab, we can try to understand how brain development is different in a child affected by a genetic cause of autism."

Stem cell tricks that could lead to new trials

The Morrow lab also takes advantage of a new methodology in stem cell biology whereby the team can extract stem cells from any tissue—without access to embryonic material. "This allows us, for the first time, to study stem cells and neurons from children who are affected by neurodevelopmental conditions like autism," says Morrow. "Prior to this methodology, there was really no way to study human neurons because of the inaccessibility of the brain."

The lab is using this technique for a variety of forms of autism. If they can identify differences in the neurons from children with a specific condition from those in typically developing children, they may be able to rescue those neurons or redirect them toward typical cell behavior. Once successful in this realm, they hope to go back to the patient who donated cells for that study and ask him or her to be a candidate in a future therapeutic trial.

Three cheers for basic science

Morrow is incredibly committed to the patient-oriented side of genetic disorders and developing more therapeutics is definitely the goal. He notes that although clinical work helps physician-scientists to define and identify critical problems, there's a lot of important work to be done in basic science—the research that reveals potential targets for treatments or interventions. "Sometimes we don't talk about it as much because it's slower," Morrow says, "but in my view, that is where the big discoveries will come. The basic science often produces insights that are unpredictable. Those are the game-changers."

So Morrow and his team are committed to doing both: the clinical work and the basic science. But it is not without the usual challenges. "If only we had all of the time and all of the trainees and all of the resources!" he says. "The basic science is harder to communicate to families who want answers sooner, but for those of us who recognize its promise, it really is an important thing to keep in the limelight. And it's something we do very well here at Brown."

His aim is true

The impact of genetics on autism research has been profound—and fast—especially with regards to diagnostic tests that have moved from the lab to the clinic in just the last 10 years. Morrow foresees a day when a child who receives a new diagnosis of autism or related neurodevelopmental condition will get a blood test that will provide a genetic diagnosis. Then, a clinician will be able to guide the child to certain behavioral and medical interventions. "A family's diagnostic odyssey will be a lot shorter and a lot more directed toward a treatment path," Morrow says. "That's the motivation for what we do in the long run, and I think there are many good reasons for hope."

Eric M. Morrow, MD, PhD, is the Mencoff Family Associate Professor of Biology, Associate Professor of Neuroscience, and Associate Professor of Psychiatry and Human Behavior at Brown University. He is also an affiliated faculty member of Brown's Carney Institute for Brain Science.