UAB Precision Medicine Identifies Possible Treatment for Rare ADNP Autism Disorder

Jan 14, 2023 at 01:18 pm by kbarrettalley

Matt Might, PhD meets with Precision Medicine Institute team members.

By Marti Webb Slay


When the Hugh Kaul Precision Medicine Institute at UAB was founded five years ago, the goal was to contribute to the effort of tailoring treatments to the characteristics of individual patients.

One case that came from the parent of a patient has already made it to clinical trials. As a result of research through an in-house artificial intelligence tool, Matt Might, PhD, who serves as director of the institute, suggested that low-dose ketamine might help treat children diagnosed with activity dependent neuroprotective protein (ADNP) disorder, the leading genetic cause of autism. Led by researchers from the Seaver Autism Center for Research and Treatment at Mount Sinai, the study suggests “that low-dose ketamine is generally safe, well-tolerated and effective to treat clinical symptoms in children diagnosed with ADNP syndrome,” according to a Mount Sinai press release.

“Not all cases of autism are linked to a single gene,” Might said. “When we do our work, we tend to split autism between those which are clearly caused by a single gene and those where there is no identifiable genetic cause. It doesn’t mean there isn’t one. It could be a mixture of several genes or genes plus environment. But ADNP is one where there is a very clear single genetic culprit.”

For proper neurological development, children need two healthy copies of the ADNP gene. Those born with ADNP syndrome have only one healthy copy of the ADNP gene, while the other doesn’t produce the ADNP protein.

Several years ago, Might met Sandra Sermone, founder of the ADNP Kids Research Foundation, whose son was the first to be diagnosed with this disorder in the U.S. Then Might met UAB’s Matt Davis, MD, who at the time was chief resident in the Department of Neurosurgery. Davis’s son Benjamin also has the ADNP disorder. At that point, Sermone asked Might if the Precision Medicine Institute could help find a solution.

This was so early in the life of the institute that the in-house AI tool mediKanren had not yet been fully developed, but as soon as the first prototypes were active, Might began running queries. The tool, which has read all of the medical literature and uses AI reasoning to make deductions, came up with a suggestion.

“Low dose ketamine could, it seems, rescue the activity of this gene,” said Might. “This particular disorder is caused by dropping about 50 percent of the normal activity in ADNP. You have one working copy and one broken copy. The strategy outlined by the AI was, ‘can you make the working copy work twice as hard?’ The strategy to do that was even simpler: Can you make twice the amount in the working copy by increasing the expression of that gene? That’s where it connected the dots from the literature to the low dose ketamine.”

Once Might found a plausible suggestion, he turned the information over to Davis, who began working with it in the context of the ADNP foundation. “They really did their homework, and they came up with all the metrics around plausibility and got it to the point where it became interesting enough to consider a clinical trial. That patient community has strong connections to Mount Sinai, so that’s where they went with it,” Might said.

The Mount Sinai press release reported: “In order to evaluate the effect of ketamine, the Mount Sinai research 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 (50 percent), fatigue (40 percent), and increased aggression (40 percent). Using parent-report instruments to assess treatment effects, ketamine was associated with improvements in a wide array of domains, including social behavior, attention deficit and hyperactivity, restricted and repetitive behaviors, and sensory sensitivities, a week after administration.”

Clinician-rated assessments also showed improvements.

Might said the goal of the patient community is to do a larger study next. “The hope is that a larger study would convince the FDA to put ADNP on the label for ketamine, so insurers would cover it.”

“I hope that physicians around Alabama with ADNP patients will contact the Precision Medicine Institute so we can connect them to the larger ecosystem on this. Likewise, if a physician is struggling with what seems to be an intractable diagnosis or just doesn’t know what to do in next steps with therapeutics, they should feel free to reach out to the Precision Medicine Institute as well.”

For more information about the Hugh Kaul Precision Medicine Institute visit

Sections: Clinical

June 2024

Jun 20, 2024 at 07:14 pm by kbarrettalley

Your May 2024 Issue of Birmingham Medical News is Here!