May 20, 2010
This is a guest post by Autism Speaks’ staff members Leanne Chukoskie, Ph.D., Jane Pickett, Ph.D., and Andy Shih, Ph.D.
One of the challenges in pursuing the causes of autism spectrum disorders is the heterogeneity of symptoms and life history of the individuals affected. On Wednesday, one day before the start of the International Meeting for Autism Research (IMFAR), meetings of two family foundations centered on specific genetic syndromes for autism moved past these challenges to offer hope for recovery.
The Phelan-McDermid Syndrome Foundation (PMSF) was one of the family foundations that hosted a meeting of international scientists, clinicians and parents to better understand PMSF. Katy Phelan, Ph.D. (Molecular Pathology Laboratory Network, TN) presented a characterization of the individuals affected, as many scientists working with animal models of this disorder have met very few, if any, persons with PMS. Dr. Phelan reviewed the cluster of symptoms present typically early in life, including a “floppy” infant, general developmental delays and poor or absent speech. She also reviewed evidence that led to the recognition that individuals with PMS had some form of mutation in the SHANK 3 gene on chromosome 22.
The meeting soon shifted to animal models and presentations from several researchers who presented greater detail about the role of the protein SHANK 3 at synapses, or junctions of neurons, which are crucial for learning and memory functions. It was shown that SHANK 3 is responsible for tying together two receptors for the common excitatory transmitter glutamate at the synapse. Through a series of careful experiments examining the structure and function of synapses when more or less SHANK 3 protein was present, Joseph Buxbaum, Ph.D. (Mount Sinai School of Medicine, NY) and colleagues learned that SHANK 3 controlled the physical connections that underlie plasticity of the synapses (the mechanism that underlies learning and memory). After achieving this detailed understanding of how the system develops and stabilizes in the animal, the next step was to attempt to rescue normal function in these animals that lack SHANK 3. A related set of receptors present on the cells (AMPA receptors) was targeted with the drug called IGF1. Injections of IGF1 into the mouse travelled across the protective barrier that encases the brain and had the desired effects on the cells, rescuing the structure and function of the synapses that had the atypical SHANK 3 proteins.
Lastly before a dinner gathering where parents scientists and clinicians can share ideas with each other more informally, Sarah Curran, Ph.D. (Kings College, London) presented on new technology that may allow the creation of stem cell lines for deeper analysis of the effect of a single individual’s mutations (the SHANK 3 gene can have mutations at several places, potentially leading to different effects on the functioning of the SHANK 3 protein) by analyzing a single complete hair from an affected person.
