Seaver Autism Center Conducts First Clinical Trial Using Insulin-like Growth Factor to Treat Subtype of Autism

Researchers at the Seaver Autism Center at the Icahn School of Medicine at Mount Sinai have received a grant from the National Institutes of Health (NIH) to study insulin-like growth factor-1 (IGF-1) in children with Phelan-McDermid Syndrome (PMS), a subtype of autism spectrum disorder (ASD). PMS, which is also known as 22q13 Deletion Syndrome, results from a mutated or missing copy of the SHANK3 gene. IGF-1 is the first medication ever used to treat PMS in a controlled clinical trial.

Children with PMS typically suffer from developmental delays, intellectual disability, motor skills deficits, delayed or absent speech, and ASD. The goal of the study is to target and improve core features of ASD, including social withdrawal and language impairment.

Led by Alexander Kolevzon, MD, Clinical Director of the Seaver Autism Center and Associate Professor of Psychiatry and Pediatrics, nine children diagnosed with PMS have already been enrolled in the trial. The NIH funding will allow for an additional 18 patients to be studied. Participants, which range in age from 5 to 12, will undergo two 12-week treatment periods in which they will receive either IGF-1 or a placebo. Every patient will receive active medication and a placebo for one treatment period.

“This clinical trial is part of a paradigm shift to develop drugs specifically to treat the core symptoms of autism, as opposed to medications that were developed for other purposes but were found to also be beneficial for the irritability and aggression that sometimes appear in autism patients,” said Joseph Buxbaum, PhD, Director of the Seaver Autism Center and Professor of Psychiatry, Genetics and Genomic Sciences, and Neuroscience at Mount Sinai. “Our study will evaluate the impact of IGF-1 when compared with placebo on autism-specific impairments in socialization and associated symptoms of language and motor disability.”

Dr. Buxbaum and Seaver Center researchers first developed a mouse model replicating the human condition and lacking a copy of the SHANK3 gene in 2010. Since then, they have discovered that deficits in nerve cell communication could be reversed after two weeks of treatment with IGF-1. What’s more, the nerve cells’ inability to adapt to stimulation, which is a key part of learning and memory, was also restored. The results from this study inspired the investigators to examine the effects of IGF-1 in humans with the same genetic disorder.

Dr. Kolevzon and his colleagues have also received funding from the Autism Science Foundation to explore the effects of IGF-1 in children with ASD who do not have SHANK3 deficiency. The goal is to expand IGF-1 studies into large, multi-centered clinical trials in an effort to include as many children as possible.

The Seaver Autism Center at Mount Sinai is one of five leading institutions to receive a $100 million, five-year grant from the National Institutes of Health to support clinical trials that determine whether oxytocin nasal spray improves social functioning in children with autism spectrum disorder. Study participants will receive oxytocin or a placebo for the first six months. Afterwards, all participants will receive the oxytocin for an additional six months. The goal of the trials is to develop novel therapies that help treat the core symptoms of ASD.

"The study is unique because it is the largest treatment study with oxytocin to date, as it will ultimately include 300 children, between the ages of 3 and 17, with an ASD diagnosis," said Dr. Kolevzon. "This is one of the first treatment studies that will focus on both verbal and nonverbal individuals and target the core symptom of social deficits in autism."