Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, London, UK.
J Intern Med. 2013 Oct;274(4):308-20. doi: 10.1111/joim.12113. Epub 2013 Aug 10.
Developing new pharmacotherapies for autism spectrum disorder (ASD) is a challenge. ASD has a complex genetic architecture, several neurobiological phenotypes and multiple symptom domains. However, new opportunities are emerging that could lead to the development of 'targeted' and individualized pharmacological interventions. Here, first we review these important new insights into the aetiology and neurobiology of ASD with particular focus on (i) genetic variants mediating synaptic structure and functioning and (ii) differences in brain anatomy, chemistry and connectivity in this condition. The characterization of the genotypic and phenotypic differences underlying ASD might in the future be invaluable for stratifying the large range of different individuals on the autism spectrum into genetically and/or biologically homogeneous subgroups that might respond to similar targeted interventions. Secondly, we propose a strategic framework for the development of targeted pharmacotherapies for ASD, which comprises several different stages in which research findings are translated into clinical applications. The establishment of animal models and cellular assays is important for developing and testing new pharmacological targets before initiating large-scale clinical trials. Finally, we present the European Autism Interventions - A Multicentre Study for Developing New Medications (EU-AIMS) Initiative, which was set up in the context of the EU Innovative Medicines Initiative as the first European platform for integrated translational research in ASD. The EU-AIMS Initiative consists of academic and industrial partners working in collaboration to deliver a more 'personalized' approach to diagnosing and treating ASD in the future.
开发用于自闭症谱系障碍（ASD）的新药物疗法是一个挑战。ASD 具有复杂的遗传结构、多种神经生物学表型和多个症状领域。然而，新的机会正在出现，这可能会导致“靶向”和个体化药物干预的发展。在这里，我们首先回顾了这些关于 ASD 的病因和神经生物学的重要新见解，特别关注：（i）介导突触结构和功能的遗传变异，以及（ii）这种情况下大脑解剖、化学和连接的差异。ASD 潜在的基因型和表型差异的特征描述，将来对于将自闭症谱系中的大量不同个体分层为具有遗传和/或生物学同质性的亚组可能是非常宝贵的，这些亚组可能对类似的靶向干预有反应。其次，我们提出了一种针对 ASD 的靶向药物疗法的战略框架，该框架包括将研究结果转化为临床应用的几个不同阶段。在开始大规模临床试验之前，建立动物模型和细胞检测对于开发和测试新的药物靶点非常重要。最后，我们介绍了欧盟自闭症干预措施——开发新药物的多中心研究（EU-AIMS）倡议，该倡议是在欧盟创新药物倡议的背景下设立的，是 ASD 综合转化研究的第一个欧洲平台。EU-AIMS 倡议由学术和工业合作伙伴共同合作，旨在为未来诊断和治疗 ASD 提供更“个性化”的方法。
