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Progress toward treatments for synaptic defects in autism

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Abstract

Autism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors. For the majority of affected individuals, the cause of ASD remains unknown, but in at least 20% of the cases, a genetic cause can be identified. There is currently no cure for ASD; however, results from mouse models indicate that some forms of the disorder could be alleviated even at the adult stage. Genes involved in ASD seem to converge on common pathways altering synaptic homeostasis. We propose, given the clinical heterogeneity of ASD, that specific 'synaptic clinical trials' should be designed and launched with the aim of establishing whether phenotype 'reversals' could also occur in humans.

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Figure 1: Time course of gene expression in the human brain and clinical features observed in patients with ASD.
Figure 2: The synaptic proteins involved in ASD and the drugs that have been tested in mouse models of ASD or in clinical trials.
Figure 3: Strategies for synaptic clinical trials in ASD.

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Acknowledgements

We thank D. DiGregorio and I. Cloez-Tayarini for critical reading of the manuscript and G. Huguet for the illustrations. This work was funded by the Institut Pasteur, the Bettencourt-Schueller foundation, Centre National de la Recherche Scientifique, University Paris Diderot, Agence Nationale de la Recherche (ANR-08-MNPS-037-01- SynGen), Neuron-ERANET (EUHF-AUTISM), the Fondation de France, the Conny-Maeva Charitable Foundation, the Cognacq Jay Foundation, the Orange Foundation, the Fondamental Foundation and the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115300, the resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007 - 2013) and European Federation of Pharmaceutical Industries and Associations companies in kind contribution.

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Correspondence to Thomas Bourgeron.

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Delorme, R., Ey, E., Toro, R. et al. Progress toward treatments for synaptic defects in autism. Nat Med 19, 685–694 (2013). https://doi.org/10.1038/nm.3193

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