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.
FINDINGS: 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.