Do animal models hold value in Autism spectrum disorder (ASD) drug discovery?

ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

KEYWORDS:

• Autism spectrum disorder
• pharmacotherapy
• animal model
• mice
• behavior

Article highlights

• Drug discovery for the core symptoms of ASD has been very challenging due to the extreme phenotypic variability, lack of a biomarker, and lack of good translational endpoints.

• ASD in human ranges in presentation and is hard to duplicate in an animal model without knowing the exact cause of ASD.

• Drugs listed show positive results in studies dealing with both the associated symptoms of ASD such as learning and memory and the diagnostic symptoms of ASD.

• Despite the translational issues modelling ASD in animals, including: extreme phenotypic variability, lack of a biomarker, and appropriate endpoints for evaluation of changes in social behavior; animal models have allowed several drugs to move on to clinical testing.

• FDA-approved drugs only treat aggression and irritability associated with ASD; other pharmacological therapies are currently under investigation for their potential to alleviate the core symptoms of ASD.

• While animals are useful as scientific models, they have disadvantages in conditions like ASD whose exact etiology is as of yet unknown; however, these models still provide information about the neurological systems that underlie social and repetitive behaviors, which is important for preclinical ASD drug research.

• The current mouse models have been invaluable in furthering our understanding of the behavioral deficits, genetic mutations, and physiology associated with ASD; this has allowed for improved bases of research and new therapeutic strategies.

This box summarizes key points contained in the article.

Declaration of interest

K Chadman declares that she is employed by The New York State Office for People with Developmental Disabilities. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Referee Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.