新規な自閉スペクトラム症中核症状治療薬の開発—臨床試験，脳画像解析，遺伝子解析の統合的アプローチ

Development of Novel Therapeutics for Core Symptoms of Autism Spectrum Disorder: An Integrative Approach of Clinical Trials, Neuroimaging, and Genomics

オキシトシンによって自閉スペクトラム症の中核症状が治療できるようになることが期待されている。しかし，単回投与では一貫して改善が報告されてきた一方，反復投与では結果が一貫しなかった。これに対し筆者は，マルチモダリティの脳画像解析や定量的表情分析を応用して自主臨床試験の結果を示し，動物実験で検証し，反復投与による改善効果の経時変化や反復投与特異的なメカニズムを示した。本論ではこれらの成果を概説する。

Abstract

Discrepancies in the efficacy between single-dose and repeated administrations of oxytocin on autism spectrum disorder (ASD) indicate a time-course change in efficacy. However, the hypothesis cannot be tested without a repeatable, objective, and quantitative measurement of the core symptoms of ASD. The author's research group comprehensively examined recently examined reported single-site exploratory (n=18, crossover) and multi-site confirmatory (n=106, parallel-group), double-blind, placebo-controlled trials of six-week intranasal oxytocin (48 IU/day) in adult males with ASD. The outcomes were statistically representative values of the objectively quantified facial expression intensity during a semi-structured social interaction in the Autism Diagnostic Observation Schedule. The quantitative facial expression analyses on data from these two independent clinical trials successfully detected and verified the therapeutic effect of repeated administrations of intranasal oxytocin on autistic features in facial expressions during social interaction. Furthermore, for the first time, the recent study demonstrated a time-course change in the efficacy: deterioration during the repetitive administration phase and preservation during the post-treatment phase. Together with our recent study regarding neurochemical mechanisms of deteriorating efficacy of oxytocin, the findings are expected to promote further development of optimized objective, quantitative, and repeatable outcome measures for autistic social deficits and to establish an optimized regimen of oxytocin treatment in ASD.