NeuroMolecular Medicine

, Volume 17, Issue 1, pp 71–82 | Cite as

NNZ-2566, a Novel Analog of (1–3) IGF-1, as a Potential Therapeutic Agent for Fragile X Syndrome

  • Robert M. J. Deacon
  • Larry Glass
  • Mike Snape
  • Michael J. Hurley
  • Francisco J. Altimiras
  • Rodolfo R. Biekofsky
  • Patricia Cogram
Original Paper


Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. Previous studies have implicated mGlu5 in the pathogenesis of the disease, and many agents that target the underlying pathophysiology of FXS have focused on mGluR5 modulation. In the present work, a novel pharmacological approach for FXS is investigated. NNZ-2566, a synthetic analog of a naturally occurring neurotrophic peptide derived from insulin-like growth factor-1 (IGF-1), was administered to fmr1 knockout mice correcting learning and memory deficits, abnormal hyperactivity and social interaction, normalizing aberrant dendritic spine density, overactive ERK and Akt signaling, and macroorchidism. Altogether, our results indicate a unique disease-modifying potential for NNZ-2566 in FXS. Most importantly, the present data implicate the IGF-1 molecular pathway in the pathogenesis of FXS. A clinical trial is under way to ascertain whether these findings translate into clinical effects in FXS patients.


Fragile X syndrome Insulin growth factor 1 NNZ-2566 Behavior Biomarkers 


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Robert M. J. Deacon
    • 1
  • Larry Glass
    • 2
  • Mike Snape
    • 3
  • Michael J. Hurley
    • 4
  • Francisco J. Altimiras
    • 5
  • Rodolfo R. Biekofsky
    • 1
  • Patricia Cogram
    • 1
    • 6
  1. 1.Neuro-DVI LLPLondonUK
  2. 2.Neuren Pharmaceuticals LtdCamberwellAustralia
  3. 3.Autism Therapeutics LtdLondonUK
  4. 4.Division of Brain Sciences, Centre for Neuroinflammation and NeurodegenerationImperial CollegeLondonUK
  5. 5.University of ChileSantiagoChile
  6. 6.Biomedicine Division, Centre for Systems BiotechnologyFraunhofer Chile Research FoundationSantiagoChile

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