Mount Sinai scientists receive NIH grant to study clinical benefit of IGF-1 in children with PMS

Aug 27 2013

Scientists 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), a promising treatment for a subtype of autism called Phelan McDermid Syndrome (PMS). The grant will allow researchers to expand upon an ongoing study assessing the clinical benefit of IGF-1 in children with this severe type of autism.

IGF-1 is a commercially-available compound for growth deficiency that is known to promote nerve cell survival as well as synaptic maturation and plasticity. The primary aim of the study is to target core features of PMS, including social withdrawal and language impairment, which will be measured using both behavioral and objective assessments. So far, nine patients have participated in a pilot study to assess safety and feasibility of IGF-1. The Seaver Autism Center team hopes to enroll 18 more participants with support from the NIH grant, in order to establish statistically significant clinical benefit of IGF-1. The NIH will provide more than $750,000 over three years to study IGF-1.

With the grant, Alex Kolevzon, MD, Clinical Director the Seaver Autism Center, will continue to enroll children ages 5 to 12 years old who have PMS in this double-blind, placebo-controlled crossover study. Patients will first receive three months of either active medication or three months of placebo. After a four-week break, patients who received active medication first will then receive three months of placebo, and patients who were first randomized to placebo will receive three months of active medication. Future trials are planned to explore the utility of IGF-1 in ASD without SHANK3 deficiency, the hallmark genetic mutation in PMS.

Dr. Kolevzon has also received a grant for $25,000 from the Autism Science Foundation to study IGF-1 as a treatment for idiopathic autism.

"IGF-1 has the potential to be effective in treating Phelan-McDermid Syndrome and other types of autism spectrum disorder," said Dr. Kolevzon. "We are very pleased that the NIH and the Autism Science Foundation have recognized this by providing us funding to continue our work in bringing this medication to our patients."

The clinical studies with IGF-1 are supported by studies in a genetically modified mouse with a mutation in SHANK3. These studies carefully examined brain function in the mice when SHANK3 was mutated, and provided preclinical evidence for a beneficial effect of IGF-1. Deficits in nerve cell communication were reversed and deficiencies in adaptation of nerve cells to stimulation, a key part of learning and memory, were restored. These studies were reported the April 27th issue of Molecular Autism.

Side effects of IGF-1 administration include low blood sugar, liver function abnormalities, and increased cholesterol and triglyceride levels. Study subjects will undergo rigorous safety screening before they are enrolled in the trial, and will be carefully monitored every two to four weeks with safety and efficacy assessments.