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

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Background:

• Autism spectrum disorder (ASD) is characterized by social communication deficits and repetitive behaviors.
• Current drug discovery for ASD faces challenges due to limited approved treatments for core symptoms.
• Animal models are vital but face limitations in face, construct, and predictive validity for ASD.

Purpose of the Study:

• To review current animal models used for testing therapeutics in ASD.
• To evaluate drugs like sulforaphane, propranolol, oxytocin, vasopressin antagonists, arbaclofen, and bumetanide in these models.

Main Methods:

• Focus on animal models with face validity for core ASD behaviors (social, repetitive).
• Assessment of therapeutic effects on modifying behaviors like learning and memory.
• Review of drug efficacy data from preclinical studies.

Main Results:

• Animal models share human research challenges: lack of biomarkers, heterogeneity, and endpoint evaluation issues.
• Despite limitations, animal model data has facilitated clinical trials for several drugs.
• Specific drugs reviewed show promise in preclinical evaluations.

Conclusions:

• Animal models, while imperfect, are instrumental in advancing ASD drug discovery.
• Continued refinement of animal models and therapeutic evaluation is essential.
• Progress in translating preclinical findings to human clinical trials is ongoing.