title: Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay.
abstract: BACKGROUND
  Haploinsufficiency of SHANK3, due to either hemizygous gene deletion (termed 22q13 deletion syndrome or Phelan-McDermid syndrome) or to gene mutation, accounts for about 0.5% of the cases of autism spectrum disorder (ASD) and/or developmental delay, and there is evidence for a wider role for SHANK3 and glutamate signaling abnormalities in ASD and related conditions. Therapeutic approaches that reverse deficits in SHANK3-haploinsufficiency may therefore be broadly beneficial in ASD and in developmental delay.
  
  
  RESULTS
  We observed that daily intraperitoneal injections of human insulin-like growth factor 1 (IGF-1) over a 2-week period reversed deficits in hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) signaling, long-term potentiation (LTP), and motor performance that we had previously reported in Shank3-deficient mice. Positive effects were observed with an IGF-1 peptide derivative as well.
  
  
  CONCLUSIONS
  We observed significant beneficial effects of IGF-1 in a mouse model of ASD and of developmental delay. Studies in mouse and human neuronal models of Rett syndrome also show benefits with IGF-1, raising the possibility that this compound may have benefits broadly in ASD and related conditions, even with differing molecular etiology. Given the extensive safety data for IGF-1 in children with short stature due to primary IGF-1 deficiency, IGF-1 is an attractive candidate for controlled clinical trials in SHANK3-deficiency and in ASD.
authors.affiliation: Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA. joseph.buxbaum@mssm.edu.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Bozdagi
authors.forename: Teresa
authors.initials: T
authors.lastname: Tavassoli
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Buxbaum