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Office of Neuroscience Research > Did you know? > Unraveling Autism (Outlook Feature Winter 2016/2017)

Unraveling Autism (Outlook Feature Winter 2016/2017)

Multifaceted approach aims to detect, treat and even reverse the disorder.
From Outlook Magazine...(page 12 in the pdf)
Like many patients visiting a doctor’s office, Kim Sebenoler started out her appointment by heading to the nearest restroom to give a urine sample. But her visit to the lab of John Constantino, MD, director of the William Greenleaf Eliot Division of Child Psychiatry, was not a typical exam. The goal was not to measure proteins in her urine or check her overall wellness.
Instead, researchers took her urine cells to replicate human brain cell function in a Petri dish. The study is one of three major approaches School of Medicine researchers are using to unravel the physical and psychological underpinnings of autism. The unique, multifaceted effort — studying genes, brain activity patterns and behavior — is giving researchers and practitioners a better understanding of the disorder, which today affects one in every 100 Americans.
The cells are helping co-investigators Constantino and neuroscientist Azad Bonni, MD, PhD, explore how brain function changes in people with autism spectrum disorder (ASD). Both researchers are international leaders — Constantino in clinical autism studies and Bonni in advancing understanding of the underlying mechanisms of brain development.
Autism is most commonly characterized by repetitive behaviors and difficulty with communication and social interaction. It has a multitude of forms, and psychologists recognize a wide spectrum of skills, symptoms and disability.
“We are engaging people across disciplines — geneticists, molecular biologists, child psychologists, neuropsychologists and human brain imaging researchers,” said Bonni, the Edison Professor of Neuroscience and chair of the Department of Neuroscience. “There is no single pathway toward treatment or discovery. It’s absolutely the case that we need multifaceted approaches. Washington University is uniquely positioned to address these challenges.”
Researchers collected urine samples from several members of the Sebenoler family, including daughter Sarah, 18, and 16-year-old identical twin boys, Mark and Jack. Kim Sebenoler is not on the autism spectrum, and Sarah has not been formally diagnosed, but the twins were diagnosed at age 3.
The researchers took the samples and separated solid material from liquid material. They isolated epithelial cells, a type of cell found in the lining of the kidneys that the body sheds all the time. From these, they produced induced pluripotent stem cells, which can become any type of cell in the body. Then, they reprogrammed the stem cells into neurons. This yielded a population of brain cells that could be studied, enabling side-by-side comparisions. Researchers are continuing to watch for variations in neuron viability and activity.
Later, the Sebenolers returned to the lab for brain imaging studies, so researchers can study activity in their entire brains, not just cells in a Petri dish. 
The family has participated in studies on autism prevalence in twins, and Kim’s son Nicholas, 9, is part of a study examining the younger siblings of children with autism. Nicholas has participated since he was a baby, and is helping researchers study the earliest possible evidence for autism-related symptoms, which may be visible as soon as 2 months of age.
Ultimately, the researchers are trying to diagnose and treat autism as early as possible, aiming to develop treatments and possibly drugs that can halt or even reverse autism-related symptoms. 
“Identifying genetic susceptibilities — and how they relate to the development of a human brain, and how genetic liabilities early in development could take a child off track — those are all of very high interest to us,” said Constantino, the Blanche F. Ittleson Professor of Psychiatry and Pediatrics and psychiatrist-in-chief at St. Louis Children’s Hospital.
He and Bonni say with early diagnosis and a suite of treatment options, doctors may be able to re-route children toward a developmentally typical track — rewiring their neurological trajectories, and eliminating or preventing autism-like behaviors. 
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