The utility of patient specific induced pluripotent stem cells for the modelling of Autistic Spectrum Disorders

Abstract

Until now, models of psychiatric diseases have typically been animal models. Whether they were to be used to further understand the pathophysiology of the disorder, or as drug discovery tools, animal models have been the choice of preference in mimicking psychiatric disorders in an experimental setting. While there have been cellular models, they have generally been lacking in validity. This situation is changing with the advent of patient-specific induced pluripotent stem cells (iPSCs). In this article, we give a methodological evaluation of the current state of the iPS technology with reference to our own work in generating patient-specific iPSCs for the study of autistic spectrum disorder (ASD). In addition, we will give a broader perspective on the validity of this technology and to what extent it can be expected to complement animal models of ASD in the coming years.

Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder

“…Autistic spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by stereotypical behaviors and by impairments in social and language skills 1. Furthermore, children with ASD have a very high prevalence of comorbid mental health conditions, such as learning disabilities, attention-deficit hyperactivity disorder, emotional disorders, and chronic tic disorder 2,3.…”

Unmet needs in paediatric psychopharmacology: Present scenario and future perspectives

“…As an example, iPSCderived neurons obtained from fibroblasts of patients with schizophrenia display decreased neurite number, reduced neuronal connectivity, and abnormal gene expression related to glutamate receptors, cytoskeletal remodelling and oxidative stress; at least some of these parameters respond to antipsychotic treatment (Brennand et al, 2012). Several experimental paradigms involving iPSC or iNEURON models of neurodevelopmental disorders have been published to date, underscoring the heuristic potential of this approach (Krey et al, 2013;Cocks et al, 2014;Doers et al, 2014). Meanwhile, several major limitations must be duly acknowledged: (a) the most consistent and reliable transformation protocols have yet to be ultimately defined; (b) the entire process has low efficiency, is cumbersome, bears high costs and takes a long time;…”

Defining Precision Medicine Approaches to Autism Spectrum Disorders: Concepts and Challenges

“…Patient-derived induced pluripotent stem cells (iPSCs) are an interesting new approach that overcomes inter-species differences, although the technology is still in need of further development. Recently, protocols have been developed to derive iPSCs from peripheral blood mononuclear cells (27) or hair roots (28). This makes sample collection significantly easier and more viable for vulnerable and larger patient groups than earlier protocols based on fibroplasts (derived from skin biopsies).…”