title: A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome.
abstract: BACKGROUND
  Autism spectrum disorder (ASD) is now understood to have multiple genetic risk genes and one example is SHANK3. SHANK3 deletions and mutations disrupt synaptic function and result in Phelan-McDermid syndrome (PMS), which causes a monogenic form of ASD with a frequency of at least 0.5% of ASD cases. Recent evidence from preclinical studies with mouse and human neuronal models of SHANK3 deficiency suggest that insulin-like growth factor-1 (IGF-1) can reverse synaptic plasticity and motor learning deficits. The objective of this study was to pilot IGF-1 treatment in children with PMS to evaluate safety, tolerability, and efficacy for core deficits of ASD, including social impairment and restricted and repetitive behaviors.
  
  
  METHODS
  Nine children with PMS aged 5 to 15 were enrolled in a placebo-controlled, double-blind, crossover design study, with 3 months of treatment with IGF-1 and 3 months of placebo in random order, separated by a 4-week wash-out period.
  
  
  RESULTS
  Compared to the placebo phase, the IGF-1 phase was associated with significant improvement in both social impairment and restrictive behaviors, as measured by the Aberrant Behavior Checklist and the Repetitive Behavior Scale, respectively. IGF-1 was found to be well tolerated and there were no serious adverse events in any participants.
  
  
  CONCLUSIONS
  This study establishes the feasibility of IGF-1 treatment in PMS and contributes pilot data from the first controlled treatment trial in the syndrome. Results also provide proof of concept to advance knowledge about developing targeted treatments for additional causes of ASD associated with impaired synaptic development and function.
authors: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1230, New York, NY 10029 USA ; Friedman Brain Institute, New York, NY USA ; Mindich Child Health Institute, New York, NY USA ; Departments of Psychiatry, New York, NY USA ; Departments of Pediatrics, New York, NY USA ; Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors: Alexander
authors: A
authors: Kolevzon
authors: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1230, New York, NY 10029 USA ; Departments of Psychiatry, New York, NY USA ; Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors: Lauren
authors: L
authors: Bush
authors: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1230, New York, NY 10029 USA ; Friedman Brain Institute, New York, NY USA ; Departments of Psychiatry, New York, NY USA ; Departments of Neuroscience, New York, NY USA ; Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors: A Ting
authors: AT
authors: Wang
authors: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1230, New York, NY 10029 USA ; Departments of Psychiatry, New York, NY USA ; Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors: Danielle
authors: D
authors: Halpern
authors: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1230, New York, NY 10029 USA ; Departments of Psychiatry, New York, NY USA ; Departments of Pediatrics, New York, NY USA ; Departments of Neurology, New York, NY USA ; Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors: Yitzchak
authors: Y
authors: Frank
authors: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1230, New York, NY 10029 USA ; Departments of Psychiatry, New York, NY USA ; Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors: David
authors: D
authors: Grodberg
authors: Departments of Pediatrics, New York, NY USA ; Departments of Endocrinology and Diabetes, New York, NY USA ; Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors: Robert
authors: R
authors: Rapaport
authors: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1230, New York, NY 10029 USA ; Departments of Psychiatry, New York, NY USA ; Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors: Teresa
authors: T
authors: Tavassoli
authors: Department of Psychology, St John's University, New York, NY USA.
authors: William
authors: W
authors: Chaplin
authors: Department of Psychiatry, Rush University Medical Center, Chicago, IL USA.
authors: Latha
authors: L
authors: Soorya
authors: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, Box 1230, New York, NY 10029 USA ; Friedman Brain Institute, New York, NY USA ; Mindich Child Health Institute, New York, NY USA ; Departments of Psychiatry, New York, NY USA ; Departments of Neuroscience, New York, NY USA ; Departments of Genetics and Genomic Sciences, New York, NY USA ; Icahn School of Medicine at Mount Sinai, New York, NY USA.
authors: Joseph D
authors: JD
authors: Buxbaum