Animal models for autism in 2017 and the consequential implications to drug discovery

ABSTRACT

Introduction: Autism spectrum disorder (ASD) is characterized by deficits in social communication and restricted interests/repetitive behaviors, for which there are currently no approved drug treatments. The core symptoms of ASD vary widely in severity and are often accompanied by other neuropsychiatric disorders. Drug discovery has been challenging because of the lack of understanding of the underlying pathophysiology of ASD as well as the heterogeneity of symptoms and symptom severity.

Areas covered: In this review, the author discusses animal models of ASD used as targets for drug discovery, focusing primarily on non-syndromic models, primarily rodents. They highlight the wide range of drug targets examined in animal models. While very little of this work has resulted in drug therapy for the behavioral symptoms of ASD yet, it has increased our knowledge of the biology of ASD that is critical for driving drug discovery and has already provided many new drug targets for investigation.

Expert opinion: The information gathered from the animal models of ASD is increasing our understanding of the underlying pathophysiology for ASD and is leading to better therapeutic targets. However, the issue of small sample size, heterogeneity within clinical samples, and a lack of replicable outcome measures must be addressed to move forward.

KEYWORDS:

• Autism spectrum disorder
• pharmacotherapy
• animal model
• mice
• rats
• voles
• social behavior
• repetitive behavior

Article highlights

• Most of the animal models of ASD that have been used in drug discovery are rodents that display behaviors with face validity for the human behavioral symptoms of ASD.

• No universal pathology is understood for ASD. Therefore, all animal models must be tested by using behaviors with face validity for the core diagnostic symptoms of ASD: deficits in social communication and restricted interests/repetitive behaviors.

• Although many drugs have been found to be effective in improving the behaviors associated with ASD in animal models, these findings have not yet been replicated in humans.

• Drug studies in humans with ASD are particularly challenging because of the heterogeneous nature of the symptoms that present in each subject, the subjective nature of the diagnostic markers, and small sample sizes, making it difficult to ascertain the effectiveness of each drug across the broader ASD population.

• The heterogeneity of symptoms presented by each person with ASD is one of the biggest challenges in drug discovery. ASD is a diagnosis that encompasses people with a wide range of abilities. Therefore, in order for drug discovery to move forward, it may be necessary to define some specific subgroups within the ASD diagnosis to find people with similar biological pathologies.

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Declaration of Interest

K Chadman has no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript has not been funded.