ketamine It may be an effective treatment for children with activity-dependent protective protein (ADNP) syndrome, a rare genetic condition linked to intellectual disability and autism spectrum disorder.
Also known as Helsmoortel-Van Der Aa syndrome, ADNP syndrome is caused by mutations in ADNP gene. Studies in animal models indicate that low-dose ketamine increases the expression of ADNP and is neuroprotective.
Intrigued by preclinical evidence, Alexander Collevzon, MD, clinical director of the Seaver Autism Center at Mount Sinai in New York, and colleagues treated 10 children with ADNP with a single low-dose (0.5 mg/kg) intravenous ketamine over 40 minutes. The children’s ages ranged from 6 to 12 years.
Using parental report tools to assess treatment effects, ketamine was associated with ‘nominally significant’ improvement in a variety of domains, including social behavior, attention deficit hyperactivity, restricted and repetitive behaviors, and sensory sensitivities.
Parents’ reports of improvement in these areas are in line with ratings rated by clinicians based on the Global Clinical Impressions Scale – Improvement.
The researchers say the findings also highlight the potential usefulness of steady-state auditory response electrophysiology and eye tracking to track change with ketamine treatment.
study was published Online on August 27 Human Genetics and Genomics (HGG) Advances.
Ketamine was generally well tolerated. There were no clinically significant abnormalities in the laboratory or cardiac monitoring, and there were no serious adverse events (AEs).
The treatment-emergent leukocytosis was mild to moderate and no child required any interventions.
The most common symptom was euphoria/absurdity in five children (50%), all of whom had a history of similar symptoms. Somnolence and fatigue occurred in four children (40%) and two of them had a history of drowsiness. aggression It was also relatively common, reported in four children (40%), all of whom were aggressive at baseline.
Decreased appetite manifested as a new onset of AE in three children (30%), increased anxiety occurred in three children (30%), and irritability, nausea/vomiting and restlessness occurred in each of two children (20%).
The researchers cautioned that the findings are intended to be “hypothesis generation”.
“We are encouraged by these findings, which provide initial support for ketamine to help reduce the negative effects of this devastating syndrome,” Kolevzon said in a press release from Mount Sinai.
Ketamine may help relieve symptoms of ADNP “by increasing expression of ADNP or by enhancing synaptic plasticity through glutamate pathways.” Medscape Medical News.
The next step, he said, is to have a “larger, placebo-controlled study approved for funding using repeated doses over a longer period of time. We are working with the FDA to obtain design approval for an investigational new drug application.”
Support for the study was provided by the ADNP Children’s Foundation and the Mood Disorders Foundation. Support for mediKanren was provided by the National Center for the Advancement of Translational Sciences, and the National Institutes of Health through the Biomedical Data Translator Program. Kolevzon is a member of the Scientific Advisory Board of Ovid Therapeutics, Ritrova Therapeutics, and Jaguar Therapeutics, and advises Acadia, Alkermes, GW Pharmaceuticals, Neuren Pharmaceuticals, Clinilabs Drug Development Corporation, and Scioto Biosciences.
Advance HGG. Posted online August 27, 2022. full text