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Cited by 242Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchGenomics and Rare Diseases

Functional recovery with recombinant human IGF1 treatment in a mouse model of Rett syndrome

Open access
Castro, Jorge, Garcia, Rodrigo I., Kwok, Showming, Banerjee, Abhishek, Petravicz, Jeremy, Woodson, Jonathan, Mellios, Nikolaos, Tropea, Daniela +1 more·2014·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1311685111PMC PMC4103342
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Abstract

Significance: Rett Syndrome is a devastating neurodevelopmental disorder that arises from mutations in the methyl-CpG binding protein 2 ( MeCP2 ) gene and has no presently available treatment. We show that levels of insulin-like growth factor-1 (IGF1) are reduced in male and female Mecp2 mutant mice. Treating male knockout mice with recombinant human IGF1 (rhIGF1) improves a range of physiological symptoms and behaviors, increases excitatory transmission and synapse density in cortical neurons, and up-regulates molecular signals underlying these deficits. Treating symptomatic female heterozygous mice also improves a range of physiological and behavioral symptoms and normalizes maturation of cortical circuits. These findings demonstrate that rhIGF1 corrects functional, structural, and molecular mechanisms downstream of MeCP2 and may be an effective therapeutic for Rett Syndrome.

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  • IGF-1 partially rescued locomotor activity, respiratory function and heart rate in Mecp2 mice.

    “Additionally, insulin-like growth factor (IGF-1) partially rescued locomotor activity, respiratory function and heart rate in Mecp2 mice [209,210].”

    From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [209]

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Cited by

Sorted by citations

Authors
Castro, J., Garcia, R. I., Kwok, S., Banerjee, A., Petravicz, J., Woodson, J., Mellios, N., Tropea, D., & Sur, M.
Affiliations
  • Massachusetts Institute of Technology (US)
  • St. James's Hospital (IE)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2014-06-23
Volume
111
Issue
27
Pages
9941-9946
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1311685111
PMC
PMC4103342
OpenAlex
W2148093798
Cited by
242
References
6
Citations by year
2026: 12 · 2025: 18 · 2024: 27 · 2023: 8 · 2022: 16 · 2021: 21 · 2020: 22 · 2019: 11 · 2018: 19 · 2017: 23 · 2016: 33 · 2015: 21 · 2014: 9 · 2013: 1
FWCI
18.83
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • Newcastle University ePrints (Newcastle Univesity)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
Rett syndrome, insulin-like growth factor I, MeCP2, Mecp2-null mice, synaptic transmission, dendritic spines, visual cortex plasticity, anxiety-like behavior, locomotor activity, lifespan, heart rate, breathing pattern, social behavior, neurodevelopmental disorders, gene therapy
MeSH terms
Animals, Behavior, Animal, Disease Models, Animal, Female, Humans, Insulin-Like Growth Factor I, Male, Mice, Inbred C57BL, Recombinant Proteins, Respiration, Visual Cortex, Signal Transduction, Rett Syndrome, Mice, Knockout, Mice, Methyl-CpG-Binding Protein 2

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