EU-AIMS: Translating Cellular and Animal Models of Synaptic Gene Deficits to Large-Scale Clinical Studies

Autism spectrum disorders are one of the most common and severe neurodevelopmental disorders yet effective treatments for the core symptoms are still lacking. This is mainly due to a) the high clinical, etiological and genetic heterogeneity between affected individuals, b) restricted knowledge of the underpinning pathophysiological mechanism(s), and c) the absence of reliable biomarkers to identify more biologically homogeneous subgroups. This panel will present examples of the integrated translational approach adopted in EU-AIMS, a large-scale public-private partnership, to identify biomarkers and new treatment targets for ASD. First, we combine patient-derived pluripotent stem cells (Price) and animal models (Steckler) of monogenic forms of ASD to understand pathophysiological mechanisms. Here, we focus on genes affecting synapse development and function (SHANKs, neurexins, neuroligins) and their downstream effects on excitatory-inhibitory balance and brain connectivity. Next, we translate this to patients using methods such as MRS. Preliminary findings from a pharmacological study validate the Glutamate/ GABA system as a tractable treatment target. Finally, we carry out linked large-scale clinical studies spanning children and adults with ASD and patients with specific synaptic gene deficits to identify biomarkers (including markers of E/I imbalances) for patient stratification that can be used in future clinical trials.
Friday, May 15, 2015: 10:30 AM-12:30 PM
Grand Ballroom A (Grand America Hotel)
Panel Chair:
E. Loth
J. Buitelaar
10:30 AM
Utility of Rodent Mutants with Altered Synaptic Signaling Pathways to Test Possible Pharmacological Interventions for ASD
T. Steckler S. Baudouin T. M. Boeckers F. Esclassan G. Gilmour G. Kumar M. E. Modi M. M. Petrinovic J. Talpos P. Scheiffele
10:55 AM
Cellular Phenotypes in Induced Pluripotent Stem Cells from Autistic Individuals
J. Price G. Cocks A. Kathuria K. Warre-Cornish R. Taylor L. Andreae
11:20 AM
EU-AIMS Clinical Research Platform to Identify Biomarkers for Patient-Stratification
E. Loth D. G. Murphy T. Banaschewski S. Baron-Cohen S. Bolte T. Bourgeron T. Charman S. Durston J. Horder M. H. Johnson E. Jones L. Mason L. O'Dwyer A. M. M. Persico J. Buitelaar
11:45 AM
Glutamate and GABA in Autism Spectrum: A Clinical in-Vivo Magnetic Resonance Spectroscopy Assay
L. A. Ajram J. Horder M. A. Mendez A. Galanopoulos L. Brennan R. Wichers D. J. Lythgoe S. C. Williams D. G. Murphy G. M. McAlonan