An open-label study evaluating the safety, behavioral, and electrophysiological outcomes of low-dose ketamine in children with ADNP syndrome

作者：Alexander Kolevzon, Tess Levy, Sarah B. Barkley, Sandra Bedrosian‐Sermone, Matthew M. Davis, Jennifer H. Foss‐Feig, Danielle Halpern, Katherine Keller, Ana Kostić, Christina Layton, Rebecca Lee, Bonnie Lerman, Matthew Might, Sven Sandin, Paige M. Siper, Laura Sloofman, Hannah E. Walker, Jessica Zweifach, Joseph D. Buxbaum · 发表于：Human Genetics and Genomics Advances · 年份：2022 · DOI：10.1016/j.xhgg.2022.100138 · 被引用次数：21 · 研究领域：Anesthesia and Neurotoxicity Research、Treatment of Major Depression、Anesthesia and Sedative Agents

Activity-dependent neuroprotective protein (ADNP) syndrome is a rare genetic condition associated with intellectual disability and autism spectrum disorder. Preclinical evidence suggests that low-dose ketamine may induce expression of ADNP and that neuroprotective effects of ketamine may be mediated by ADNP. The goal of the proposed research was to evaluate the safety, tolerability, and behavioral outcomes of low-dose ketamine in children with ADNP syndrome. We also sought to explore the feasibility of using electrophysiological markers of auditory steady-state response and computerized eye tracking to assess biomarker sensitivity to treatment. This study utilized a single-dose (0.5 mg/kg), open-label design, with ketamine infused intravenously over 40 min. Ten children with ADNP syndrome ages 6 to 12 years were enrolled. Ketamine was generally well tolerated, and there were no serious adverse events. The most common adverse events were elation/silliness (50%), fatigue (40%), and increased aggression (40%). Using parent-report instruments to assess treatment effects, ketamine was associated with nominally significant improvement in a wide array of domains, including social behavior, attention deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities, a week after administration. Results derived from clinician-rated assessments aligned with findings from the parent reports. Overall, nominal improvement was evident based on the Clinical Global Im...