Researchers take the first steps towards treatment of neurodevelopmental disorders
Photo supplied by Watson.
Neural stem cells capable of repairing the brain’s white matter could be used to treat neurodevelopmental disorders such as autism, schizophrenia, ADHD and dyslexia, according to University of Alberta PhD student, Adrianne Watson. She believes her team has taken the first step towards developing a therapeutic agent for these disorders.
“Although we’ve come a long way in terms of pharmacological and behavioural interventions for these kinds of neurodevelopmental disorders, we still don’t have any treatment that can address the underlying issues in the brain structures that cause these issues,” says Watson.
While grey matter is primarily nerve cells—the main signalling cells in the brain, Watson explains white matter is essential for nerve cells to properly communicate with one another. Aberrations in brain communication and connectivity are believed to be the main underlying pathology in pediatric neurodevelopmental disorders, which affect around five per cent of all Canadian children.
“An emerging way to restore proper brain connectivity is to repair the white matter by using neural stem cells to create the building blocks of white matter—oligodendrocytes—which produce myelin,” says Watson.
Myelin, an insulating layer that forms around nerves, allows quick and efficient communication along the nerve cells.
“If we can understand what causes neural stem cells to become oligodendrocytes in a healthy developing brain, we can begin to develop therapies that engage existing neural stem cells for the treatment—or even prevention—of cognitive and behavioural deficiencies seen in children with these disorders.”
Watson, along with her supervisor Anastassia Voronova, a Canada Research Chair in Neural Stem Cell Biology and assistant professor in the Department of Medical Genetics, thinks they’ve found a pathway for developing a therapeutic agent—an immunological molecule present in the developing brain called fractalkine.
“Fractalkine is a signalling molecule, like insulin or adrenalin, that carries different messages to cells and tells them to act in a certain way,” explains Watson. “Previously, most of the work done with fractalkine showed that it was an inflammatory signalling molecule that carries inflammatory messages during injury or disease.”
Watson’s groundbreaking research, published in Stem Cell Reports, showed for the first time that fractalkine can actually communicate with existing postnatal and adult neural stem cells and encourage them to become the cells that make white matter.
“When fractalkine signalling was blocked, the ability of neural stem cells to transform into myelin-producing oligodendrocytes was diminished, meaning that proper cell communication wasn’t happening,” says Watson.
Now that Watson and Voronova have established how fractalkine functions in healthy brain development, they will examine how fractalkine behaves in abnormal brain development.
“We will look at how a mutation in the fractalkine receptor affects brain development, and also use administration of fractalkine to determine if we can actually improve myelin production,” says Watson.
Watson, who has a personal connection to her research, hopes that her work leads to the development of future treatments for children with neurodevelopmental disorders, not only to improve their lives and ability to function but also to help their families and caregivers.
“My family is quite affected by schizophrenia-like disorders,” says Watson. “Learning that we might be contributing to a treatment to alleviate some of the cognitive and behavioural symptoms and helping families is really exciting.”
Adrianne Watson, a PhD candidate in the department of medical genetics, is supervised by Anastassia Voronova, a member of both the Neuroscience and Mental Health Institute (NMHI) and WCHRI. Watson’s graduate studentship project is funded by the Stollery Children’s Hospital Foundation through WCHRI.
