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Drug discovery for autism spectrum disorder: challenges and opportunities
Anirvan Ghosh1, Aubin Michalon1,2, Lothar Lindemann1, Paulo Fontoura1 and Luca Santarelli1
Abstract | The rising rates of autism spectrum disorder (ASD) and the lack of effective medications to treat its core symptoms have led to an increased sense of urgency to identify therapies for this group of neurodevelopmental conditions. Developing drugs for ASD, however, has been challenging because of a limited understanding of its pathophysiology, difficulties in modelling the disease invitro and invivo, the heterogeneity of symptoms, and the dearth of prior experience in clinical development. In the past few years these challenges have been mitigated by considerable advances in our understanding of forms of ASD caused by single-gene alterations, such as fragile X syndrome and tuberous sclerosis. In these cases we have gained insights into the pathophysiological mechanisms underlying these conditions. In addition, they have aided in the development of animal models and compounds with the potential for disease modification in clinical development. Moreover, genetic studies are illuminating the molecular pathophysiology of ASD, and new tools such as induced pluripotent stem cells offer novel possibilities for drug screening and disease diagnostics. Finally, large-scale collaborations between academia and industry are starting to address some of the key barriers to developing drugs for ASD. Here, we propose a conceptual framework for drug discovery in ASD encompassing target identification, drug profiling and considerations for clinical trials in this novel area.
F. HoffmannLa Roche, pRED, Pharma Research and Early Development, DTA Neuroscience, Grenzacherstrasse 124, 4070 Basel, Switzerland.
Present address: Neurimmune Holding, Wagistrasse 13, 8952 Schlieren, Switzerland. Correspondence to A.G.: [email protected] doi:10.1038/nrd4102
The term autism was introduced in 1938 by Hans Asperger1
when he was investigating a type of autism spectrum disorder (ASD) now known asAspergers syndrome. Independently, in 1943 Leo Kannerused the termautism in a report in which he described 11 children with considerable behavioural similarities, including autistic aloneness and insistence on sameness2. Today, the diagnostic category of ASD represents a neurodevelopmental condition that is characterized by the presence of persistent deficits in social interaction and communication, as well as restricted social interests and repetitive behaviours. These core symptoms are usually detectable and diagnosed in children by 3years of age. The symptoms are highly variable in severity...