Background

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with a complex underlying genetic architecture. There are currently no known pharmacologic treatments for the core ASD symptoms of social deficits and restricted/ repetitive behavior. However, there are dozens of clinical trials currently underway that are testing the impact of novel and existing agents on core and associated symptoms in ASD.

Methods

We present a narrative synthesis of the historical and contemporary challenges to drug discovery in ASD. We then provide an overview of novel treatments currently under investigation from a genomics and systems biology perspective.

Results

Data driven network and cluster analyses suggest alterations in transcriptional regulation, chromatin remodelling, synaptic transmission, neuropeptide signalling, and/or immunological mechanisms may contribute to or underlie the development of ASD. Agents and upcoming trials targeting each of the above listed systems are reviewed.

Conclusion

Identifying effective pharmacologic treatments for the core and associated symptom domains in ASD will require further collaboration and innovation in the areas of outcome measurement, biomarker research, and genomics, as well as systematic efforts to identify and treat subgroups of individuals with ASD who may be differentially responsive to specific treatments.

中文翻译：

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基于基因组学和系统生物学的自闭症谱系障碍新疗法

背景

自闭症谱系障碍（ASD）是一种高度异质的神经发育障碍，具有复杂的潜在遗传结构。目前尚无已知的药物治疗可用于治疗社交缺陷和限制/重复行为的核心 ASD 症状。然而，目前正在进行的数十项临床试验正在测试新型和现有药物对 ASD 核心和相关症状的影响。

方法

我们对 ASD 中药物发现的历史和当代挑战进行了叙述性综合。然后，我们从基因组学和系统生物学的角度概述了目前正在研究的新疗法。

结果

数据驱动的网络和聚类分析表明，转录调控、染色质重塑、突触传递、神经肽信号传导和/或免疫机制的改变可能有助于或成为 ASD 发展的基础。审查了针对上述每个系统的代理和即将进行的试验。

结论

为 ASD 的核心和相关症状领域确定有效的药物治疗将需要在结果测量、生物标志物研究和基因组学领域进一步合作和创新，以及系统地努力识别和治疗可能存在差异的 ASD 个体亚组对特定治疗有反应。