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. 2014 Dec 12;5(1):54.
doi: 10.1186/2040-2392-5-54. eCollection 2014.

A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome

Alexander Kolevzon  1 , Lauren Bush  2 , A Ting Wang  3 , Danielle Halpern  2 , Yitzchak Frank  4 , David Grodberg  2 , Robert Rapaport  5 , Teresa Tavassoli  2 , William Chaplin  6 , Latha Soorya  7 , Joseph D Buxbaum  8
Affiliations

A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome

Alexander Kolevzon et al. Mol Autism. .

Erratum in

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.

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Figures

Figure 1
Figure 1
ABC-SW score between baseline and week 12 of drug or placebo. (A) Change in ABC-SW score between baseline and week 12 of drug or placebo for 9 subjects. In this and all subsequent figures, treatment condition (drug versus placebo) was combined across treatment phases. Error bars = ±1 SE. (B) Mean change in ABC-SW score between baseline and week 12 of drug or placebo. P = 0.040; error bars = ±1 SE. ABC-SW = Aberrant Behavior Checklist Social Withdrawal subscale; SE = standard error.
Figure 2
Figure 2
RBS-R Restricted Behavior score between baseline and week 12 of drug or placebo. (A) Change in RBS-R Restricted Behavior score between baseline and week 12 of drug or placebo. (B) Mean change in RBS-R Restricted Behavior score between baseline and week 12 of drug or placebo. P = 0.042; error bars = ±1 SE. RBS-R = Repetitive Behavior Scale-Revised. SE = standard error. The star reflects the p value and notes the significance.
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