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Brief Report: Initial Trial of Alpha7-Nicotinic Receptor Stimulation in Two Adult Patients with Autism Spectrum Disorder

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Abstract

Abnormalities in CHRNA7, the alpha7-nicotinic receptor gene, have been reported in autism spectrum disorder. These genetic abnormalities potentially decrease the receptor’s expression and diminish its functional role. This double-blind, placebo-controlled crossover study in two adult patients investigated whether an investigational receptor-specific partial agonist drug would increase the inhibitory functions of the gene and thereby increase patients’ attention. An electrophysiological biomarker, P50 inhibition, verified the intended neurobiological effect of the agonist, and neuropsychological testing verified a primary cognitive effect. Both patients perceived increased attention in their self-ratings. Alpha7-nicotinic receptor agonists, currently the target of drug development in schizophrenia and Alzheimer Disease, may also have positive clinical effects in autism spectrum disorder.

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Acknowledgments

Funding for the study came from an unrestricted gift from the Institute of Children’s Mental Disorders.

Author Contributions

A.O. developed the protocol and conducted the study. A.B.-S developed the neurocognitive rationale for the study, selected the psychological assessments, and evaluated the patients. L.J developed the drug formulation and randomization. W.R.K. discovered and synthesized the drug substance. R.F. developed the neurobiological rationale for the study.

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Authors and Affiliations

  1. Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO, USA

    Ann Olincy, Audrey Blakeley-Smith, Lynn Johnson & Robert Freedman

  2. Department of Behavioral Pediatrics and JFK Partners, Children’s Hospital Colorado, Aurora, CO, USA

    Audrey Blakeley-Smith

  3. Department of Pharmacology and Toxicology, University of Florida School of Medicine, Gainesville, FL, USA

    William R. Kem

Authors
  1. Ann Olincy
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  2. Audrey Blakeley-Smith
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  3. Lynn Johnson
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  4. William R. Kem
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  5. Robert Freedman
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Corresponding author

Correspondence to Robert Freedman.

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Ethical Approval

All procedures performed in studies involving human participants were in accord with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

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Olincy, A., Blakeley-Smith, A., Johnson, L. et al. Brief Report: Initial Trial of Alpha7-Nicotinic Receptor Stimulation in Two Adult Patients with Autism Spectrum Disorder. J Autism Dev Disord 46, 3812–3817 (2016). https://doi.org/10.1007/s10803-016-2890-6

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  • DOI: https://doi.org/10.1007/s10803-016-2890-6

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