Results from a small study suggest that low-dose ketamine could be an effective treatment for children living with ADNP syndrome, otherwise known as Helsmoortel-VanDerAa syndrome.
ADNP is a rare neurodevelopmental disorder caused by mutations in the activity dependent neuroprotective protein (ADNP) gene.
The ADNP gene affects brain formation, development and function, and the protein produced from it helps control the expression of other genes. ADNP mutations are one of the most common single-gene causes of autism.
Ketamine was approved in the United States in 1970 and is used for anesthesia and pain management, and more recently as a treatment for depression. Studies in animal models suggest that low-dose ketamine may be neuroprotective and increase expression of the ADNP gene.
Findings from this most recent study, led by researchers from the Seaver Autism Center for Research and Treatment at Mount Sinai and published online in Human Genetics and Genomic Advances, suggest that low-dose ketamine is generally safe, well-tolerated and effective to treat clinical symptoms in children diagnosed with ADNP syndrome.
Alexander Kolevzon, MD, Clinical Director of the Seaver Autism Center, commented: “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 behavioural outcomes of low-dose ketamine in children with the syndrome.
“We also sought to explore the feasibility of using electrophysiological biomarkers and computerized eye-tracking to assess sensitivity to treatment.”
In order to evaluate the effect of ketamine, the team used a single-dose (0.5mg/kg), open-label design, with ketamine infused intravenously over 40 minutes.
Ten children with ADNP syndrome, ages six to 12 years, were enrolled. They found ketamine was generally well-tolerated, and there were no serious adverse events.
The most common adverse events were elation/silliness at 50 per cent), fatigue at 40 per cent, and increased aggression at 40 per cent.
Using parent-report instruments to assess treatment effects, ketamine was associated with improvements in a wide array of domains, including social behaviour, attention deficit and hyperactivity, restricted and repetitive behaviours and sensory sensitivities, a week after administration.
The results also highlight the potential of assessing early changes in social attention with computerized eye-tracking and the electrophysiological measurement of a listening task known as auditory steady-state response.
Kolevzon continued: “We are encouraged by these findings, which provide preliminary support for ketamine to help reduce negative effects of this devastating syndrome.
“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.”
