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Leveraging a translational research approach to drive diagnostic and treatment advances for autism

Molecular Psychiatry volume 27, pages 2650–2658 (2022)Cite this article

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Abstract

Autism spectrum disorder (ASD) is a prevalent and poorly understood neurodevelopmental disorder. There are currently no laboratory-based diagnostic tests to detect ASD, nor are there any disease-modifying medications that effectively treat ASD’s core behavioral symptoms. Scientific progress has been impeded, in part, by overreliance on model organisms that fundamentally lack the sophisticated social and cognitive abilities essential for modeling ASD. We therefore saw significant value in studying naturally low-social rhesus monkeys to model human social impairment, taking advantage of a large outdoor-housed colony for behavioral screening and biomarker identification. Careful development and validation of our animal model, combined with a strong commitment to evaluating the translational utility of our preclinical findings directly in patients with ASD, yielded a robust neurochemical marker (cerebrospinal fluid vasopressin concentration) of trans-primate social impairment and a first-in-class medication (intranasal vasopressin) shown in a small phase 2a pilot trial to improve social abilities in children with ASD. This translational research approach stands to advance our understanding of ASD in a manner not readily achievable with existing animal models, and can be adapted to investigate a variety of other human brain disorders which currently lack valid preclinical options, thereby streamlining translation and amplifying clinical impact more broadly.

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Fig. 1: ASD research strategy for streamlined translation and clinical impact.

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Acknowledgements

I am grateful to the research collaborators who thought with me and made this body of work possible. They include: Joe Garner, Ozge Oztan, John Capitanio, Antonio Hardan, Elliott Sherr, Kate Talbot, Jennifer Phillips, Sonia Partap, Valentina Sclafani, Sue Swedo, John Constantino, Annie Penn, Dean Carson, Dan Bowling, Laura Del Rosso, Robin Libove, and Adam Myers. I also thank my departmental colleagues Carl Feinstein, David Hong, and Lawrence Fung for their thoughtful discussions on both ASD and the benefits and limitations of animal models. This work has been supported by the National Institutes of Health (R01HD091972; R01HD087048; R21HD083629; R21MH100387; R21HD079095; P51OD011107; R24OD010962), the Simons Foundation (SFARI#s 627146; 342873; 274472; 93231), the Department of Défense (W81XWH-21-1-0210), several family foundations (Weston Havens Foundation; Mosbacher Family Fund for Autism Research; The Yani Calmidis Memorial Fund for Autism Research; The Gupta Foundation; The Peter and Stacy Sullivan Foundation), and Stanford University (Department of Psychiatry; Maternal Child Health Research Institute; Bio-X NeuroVentures Program; Lucile Packard Children’s Hospital Pediatric Neurosciences Fund; The Katherine D. McCormick Fund; Wu Tsai Neurosciences Institute).

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  1. Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, 94305, USA

    Karen J. Parker

  2. Department of Comparative Medicine, Stanford University, Stanford, CA, 94305, USA

    Karen J. Parker

  3. California National Primate Research Center, Davis, CA, 95616, USA

    Karen J. Parker

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KJP conceptualized, investigated, wrote, reviewed, and edited this manuscript.

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The Board of Trustees of the Leland Stanford Junior University has filed patent applications related to data reviewed herein: PCT/US2019/019029 (“Methods for diagnosing and determining severity of an autism spectrum disorder”) and PCT/US2019/041250 (“Intranasal Vasopressin Treatment for Social Deficits in Children with Autism”). These patents have not been granted, nor licensed, and the author is not receiving any financial compensation at this time.

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Parker, K.J. Leveraging a translational research approach to drive diagnostic and treatment advances for autism. Mol Psychiatry 27, 2650–2658 (2022). https://doi.org/10.1038/s41380-022-01532-8

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