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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Molecular Autism 1/2014

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

Molecular Autism > Ausgabe 1/2014
Alexander Kolevzon, Lauren Bush, A Ting Wang, Danielle Halpern, Yitzchak Frank, David Grodberg, Robert Rapaport, Teresa Tavassoli, William Chaplin, Latha Soorya, Joseph D Buxbaum
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​2040-2392-5-54) contains supplementary material, which is available to authorized users.
An erratum to this article is available at http://​dx.​doi.​org/​10.​1186/​s13229-015-0025-0.

Competing interests

The Icahn School of Medicine at Mount Sinai and Dr. Joseph Buxbaum hold a shared patent for insulin-like growth factor-1 in the treatment of Phelan-McDermid syndrome. No non-financial conflicts of interest exist for any of the authors.

Authors’ contributions

AK, LB, and ATW participated in study design, data collection, data analysis, and manuscript preparation. TT participated in data collection, data analysis, and manuscript preparation. DH, YF and DG participated in data collection and manuscript preparation. RR participated in study design, data analysis, and manuscript preparation. WC participated in data analysis. LS and JDB participated in study design and manuscript preparation. All authors read and approved the manuscript.



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.


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.


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.


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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