Sandra Sermone and her son, Tony, who has ADNP syndrome. Mrs. Sermone founded the ADNP Kids Research Foundation, which is funding Mount Sinai’s phase 2 clinical trial into the safety and efficacy of ketamine as a potential treatment.
Ketamine, an anesthetic medication that has also been approved for use in severe depression, is now offering promise to children with a form of autism known as ADNP syndrome, or Helsmoortel-Van Der Aa syndrome. Ten children, ages 5 to 12, will soon take part in a clinical trial conducted by the Seaver Autism Center for Research and Treatment at Mount Sinai to determine whether ketamine is safe and well tolerated, and able to help compensate for the neuropsychiatric deficits that stem from missing a copy of the ADNP gene.
This will be the first clinical trial launched for ADNP syndrome, which was identified in 2015. It is a testament to the dedication of parents and physicians at the Seaver Autism Center, and the potential of artificial intelligence (AI) in helping advance treatment research in rare disorders.
Ketamine and several other existing drugs were identified by an AI tool, mediKanren. It was created at the University of Alabama by a colleague of Matthew C. Davis, MD, whose child has ADNP syndrome. Dr. Davis and another parent, Sandra Sermone, investigated ketamine in relation to ADNP within the existing scientific literature and found that it upregulated expression of the gene. With this and other relevant clinical data in hand, they filed for intellectual property protection. Then Mrs. Sermone brought the information to leaders of the Seaver Autism Center, who agreed that it was worth further investigation. Alexander Kolevzon, MD, Clinical Director of the Seaver Autism Center applied to the U.S. Food and Drug Administration for permission to proceed with a clinical trial and received approval.
“We think ketamine has potential and that it’s safe, so we’re very excited about it,” says Mrs. Sermone, who founded the ADNP Kids Research Foundation in 2016. The Foundation recently ran a “virtual” fundraising effort that raised more than $150,000 in six weeks that will be used to finance the entire phase 2 clinical trial and begin to lay the groundwork for a possible phase 3 study.
Approximately 275 children worldwide have been diagnosed with the syndrome, which often is accompanied by other complex health issues of the heart and brain. “I am so grateful for the team at Mount Sinai. I’ve never seen a group more dedicated to working with patient groups,” she adds. “Ketamine is a repurposed drug, so if it shows efficacy we can hopefully move quickly into a larger, phase 3 clinical.”
Ana Kostic, PhD, Director of Drug Discovery and Development at the Seaver Autism Center, says, “Ketamine has been used for many decades. We know a lot about the molecule and its safety profile, and now to find new uses for it through scientific discovery is amazing.”
Since ADNP is very important for the development and function of the central nervous system, the ability to restore its functionality would be extremely beneficial.
Dr. Kolevzon says each of the children enrolled in the clinical trial will receive a single infusion of ketamine over a period of 40 minutes and will be monitored over the course of four weeks to assess improvement. In addition to determining its safety and tolerability, he says, “we are also really interested in clinical improvement. Kids with ADNP have a lot of sensory sensitivities that we can measure with different tools, such as electrophysiology.” This would enable the researchers to “see whether there are changes in the electrical patterns in the brain in response to ketamine, and that might give us insight into potential biomarkers. These children have language problems, behavioral problems, and sleep problems. There are a lot of issues that go along with ADNP syndrome that we’re hoping to potentially address.”
The promise of ketamine may also extend to larger populations of individuals with autism who do not necessarily have ADNP syndrome, according to Dr. Kostic. “It could have beneficial effects in people who don’t have the same mutation but who have similar deficits.”
Access to high-quality genetic technology has become increasingly affordable over the past several years and has enabled more families to receive accurate and earlier diagnoses of many disorders, including autism. In most cases, the younger a child receives intervention, the better their chances of improvement. Earlier diagnoses, and a potential treatment such as ketamine, provide Mrs. Sermone and other committed parents with hope.
“It’s incredibly important because, currently, there isn’t one single treatment for our children with ADNP syndrome,” says Mrs. Sermone. “Our kids don’t produce enough of the ADNP protein. It’s like they’re running on half a tank of gas. To improve the quality of their lives—for us, that would be amazing.”