Ketamine may be effective in treating children with ADNP syndrome

Low-dose ketamine was generally safe, well-tolerated and effective in treating clinical symptoms in a small group of children with activity-dependent neuroprotective protein syndrome, researchers reported.

“Activity-dependent neuroprotective protein (ADNP) syndrome is a rare genetic condition associated with intellectual disability and autism spectrum disorder,” Alexander Kolevzon, MD, a pediatric psychiatrist and clinical director of the Seaver Autism Center for Research and Treatment at Mount Sinai Icahn School of Medicine in New York, and colleagues wrote in Human Genetics and Genomics Advances.

According to a press release from Mount Sinai, the ADNP gene affects brain formation, development and function, and its mutations are one of the most common single-gene causes of autism.

Preclinical evidence suggests that low-dose ketamine may induce expression of ADNP, and that neuroprotective effects of ketamine may by mediated by ADNP, the authors wrote.

“We were intrigued by the preclinical evidence suggesting that low-dose ketamine may increase levels of the ADNP protein and compensate for its loss in ADNP syndrome, so we designed this study to evaluate the safety, tolerability and behavioral outcomes of low-dose ketamine in children with the syndrome,” Kolevzon said in the release.

Kolevzon and colleagues assessed 10 children with ADNP syndrome, aged 6 to 12 years, who were given a single dose (0.5 mg/kg) of IV ketamine infused over 40 minutes. Researchers conducted clinical visits for safety, clinical outcomes and biomarker assessments at baseline and weeks 1, 2 and 4. Parent-rated questionnaires, clinician-rated measures and objective measures were used to assess treatment effects and patient outcomes.

According to the results, ketamine was associated with improvements in social behaviors, ADHD symptoms, restricted and repetitive behaviors, and sensory reactivity. The most common adverse events reported were elation or silliness (50%), fatigue (40%) and increased aggression (40%).

“We are encouraged by these findings, which provide preliminary support for ketamine to help reduce negative effects of this devastating syndrome,” Kolevzon said. “Future studies using a placebo-controlled design and studying the effects of repeated dosing over a longer duration of time and in a larger cohort of participants are needed before ketamine is used clinically, but our study is a promising first step in that process.”

Reference:

• New study suggests ketamine may be an effective treatment for children with ADNP Syndrome. https://www.mountsinai.org/about/newsroom/2022/new-study-suggests-ketamine-may-be-an-effective-treatment-for-children-with-adnp-syndrome. Published Sept. 6, 2022. Accessed Sept. 7, 2022.