Chances are you know someone with autism spectrum disorder, or have, at the very least, been exposed to it in the media. Films like I am Sam, Rain Main, What’s Eating Gilbert Grape and well-publicized stories such as that of Hollywood starlet Jenny McCarthy and her fight for her autistic son all show different sides of this complex disease. Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately one in every 165 children in Canada. It is characterized by impaired social interaction and communication, unusual or repetitive behaviours, and cognitive delays. Despite the widespread impact of ASDs, it is not well understood and there are no cures available (despite what Ms McCarthy might say).
In my own work, I have been studying the different genetic variants that contribute to the development of ASD. It can be a difficult and challenging field of research, due in part to the unavailability of live patient neurons and the lack of normal and ASD post mortem brains for research. Some murine models exist, but these can have technical complications and may not accurately reflect the human disease, since there are areas present in the human brain that are not present in the mouse brain. These issues may now be addressed by the use of induced pluripotent stem cells (iPSCs).
In recent years, induced pluripotent stem cells have emerged as a candidate for ASD research and, possibly, treatment. Since iPSCs retain the original genetic information of the parent cells, the phenotypes of cells generated from iPSCs also represent those shown by the parent cells. Using iPSCs engineered from patient samples provides a mechanism for formulating a cellular model of human disease for basic and translational research. Unlike traditional models, which may require a colony of mice or donated human tissues, the use of iPSCs only requires an initial skin biopsy or blood sample, for example. From there, reprogrammed cells are directed to differentiate into neurons, after which they can be studied for their connectivity, synaptic activity, or used in drug screens.
Results have already begun to emerge from this novel use of iPSCs in ASD research. Molecular Pyschiatry recently reported the discovery of neurophysiological alterations relating to Rett syndrome, an autism spectrum disorder involving the grey matter of the brain. It is caused by abnormalities in a binding protein called MeCP2. Like other types of ASD, it is challenging to model. Previous attempts at modelling this disease used MeCP2 deficient mice. However, this approach is problematic because these mice are difficult to breed. The work from the University of Toronto shows that MeCP2-deficient iPSCs possess the same deficits seen in primary cells, thereby showing that iPSCs can be used to help identify important steps in the progression of Rett syndrome. It’s a first and crucial finding that, in the future, may aid in the discovery of drug compounds that could address the protein abnormality.
The use of iPSCs in disease modelling and research is still in the early stages. Before it can progress to clinical applications, improvements need to be made in standardization of protocols and reduction of cell line variability. Like any new technology, optimizations will no doubt occur parallel to increased usage. With further research and development, it may one day provide the key to developing effective therapies for treating autism spectrum disorder.