动物模型在自闭症谱系障碍(ASD)药物发现中有价值吗?
Do animal models hold value in Autism spectrum disorder (ASD) drug discovery?
机构信息
a Behavioral Pharmacology Laboratory, NYS Office for People With Developmental Disabilities , Institute for Basic Research in Developmental Disabilities , Staten Island , NY , USA.
b Center for Developmental Neuroscience and Developmental Disabilities , City University of New York, College of Staten Island , Staten Island , NY , USA.
出版信息
Expert Opin Drug Discov. 2019 Aug;14(8):727-734. doi: 10.1080/17460441.2019.1621285. Epub 2019 May 27.
: Autism spectrum disorder (ASD) defines impairments in a broad range of behaviors in two domains, social communication and repetitive behaviors and/or restricted interests. Drug discovery is ongoing for ASD, but no drugs have been approved for the core behaviors. Animal models are invaluable for drug discovery, but are limited by the face, construct, and predictive validity for ASD. The genetic construct validity of animal models has provided potential targets including biological events early in development which are indeed challenging to treat pharmacologically. : The focus of this review is on the current models for ASD being used to test potential therapeutics. Drugs reviewed include sulforaphane, propranolol, oxytocin, vasopressin antagonists, arbaclofen, and bumetanide, that have been evaluated on behaviors with face validity for both the core behaviors of ASD, social and repetitive behaviors, and the modifying behaviors including learning and memory. : Animal models for the core symptoms of ASD have suffered from the same problems hampering research in humans, including lack of a biomarker, heterogeneity of symptom severity, and appropriate endpoints for evaluation. Despite this, the data from animal models has allowed several drugs to move on to clinical testing.
自闭症谱系障碍 (ASD) 定义了两个领域中广泛行为的损伤,即社交沟通和重复行为和/或受限兴趣。ASD 的药物发现正在进行中,但没有药物被批准用于核心行为。动物模型对于药物发现非常宝贵,但受到 ASD 的表面、结构和预测有效性的限制。动物模型的遗传结构有效性为潜在靶点提供了可能性,包括发育早期的生物学事件,这些事件实际上在药理学上难以治疗。本综述的重点是目前用于测试潜在治疗方法的 ASD 模型。综述中包括了已在具有 ASD 的核心行为(社交和重复行为)以及修饰行为(学习和记忆)的表面有效性的行为上进行了评估的药物,包括萝卜硫素、普萘洛尔、催产素、加压素拮抗剂、阿巴氯芬和布美他尼。ASD 核心症状的动物模型也存在着阻碍人类研究的同样问题,包括缺乏生物标志物、症状严重程度的异质性以及适当的评估终点。尽管如此,动物模型的数据已经允许几种药物进入临床测试。