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Treatment of type 2 diabetes with the designer cytokine IC7Fc

Author

Listed:
  • Maria Findeisen

    (The Garvan Institute of Medical Research)

  • Tamara L. Allen

    (Baker Heart & Diabetes Institute)

  • Darren C. Henstridge

    (Baker Heart & Diabetes Institute)

  • Helene Kammoun

    (Baker Heart & Diabetes Institute)

  • Amanda E. Brandon

    (The Garvan Institute of Medical Research
    University of Sydney)

  • Laurie L. Baggio

    (University of Toronto)

  • Kevin I. Watt

    (The University of Melbourne)

  • Martin Pal

    (The Garvan Institute of Medical Research
    The University of Melbourne)

  • Lena Cron

    (The Garvan Institute of Medical Research)

  • Emma Estevez

    (The Garvan Institute of Medical Research)

  • Christine Yang

    (Baker Heart & Diabetes Institute)

  • Greg M. Kowalski

    (Baker Heart & Diabetes Institute
    Deakin University)

  • Liam O’Reilly

    (The Garvan Institute of Medical Research)

  • Casey Egan

    (Monash University)

  • Emily Sun

    (Flinders University)

  • Le May Thai

    (The Garvan Institute of Medical Research)

  • Guy Krippner

    (Baker Heart & Diabetes Institute)

  • Timothy E. Adams

    (CSIRO Manufacturing)

  • Robert S. Lee

    (Baker Heart & Diabetes Institute)

  • Joachim Grötzinger

    (Christian-Albrechts-Universität zu Kiel)

  • Christoph Garbers

    (Otto von Guericke University)

  • Steve Risis

    (Baker Heart & Diabetes Institute)

  • Michael J. Kraakman

    (Baker Heart & Diabetes Institute)

  • Natalie A. Mellet

    (Baker Heart & Diabetes Institute)

  • James Sligar

    (The Garvan Institute of Medical Research)

  • Erica T. Kimber

    (The Garvan Institute of Medical Research)

  • Richard L. Young

    (University of Adelaide)

  • Michael A. Cowley

    (Monash University)

  • Clinton R. Bruce

    (Baker Heart & Diabetes Institute
    Deakin University)

  • Peter J. Meikle

    (Baker Heart & Diabetes Institute)

  • Paul A. Baldock

    (The Garvan Institute of Medical Research)

  • Paul Gregorevic

    (The University of Melbourne)

  • Trevor J. Biden

    (The Garvan Institute of Medical Research)

  • Gregory J. Cooney

    (The Garvan Institute of Medical Research
    University of Sydney)

  • Damien J. Keating

    (Flinders University)

  • Daniel J. Drucker

    (University of Toronto)

  • Stefan Rose-John

    (Christian-Albrechts-Universität zu Kiel)

  • Mark A. Febbraio

    (The Garvan Institute of Medical Research
    Baker Heart & Diabetes Institute
    Monash University)

Abstract

The gp130 receptor cytokines IL-6 and CNTF improve metabolic homeostasis but have limited therapeutic use for the treatment of type 2 diabetes. Accordingly, we engineered the gp130 ligand IC7Fc, in which one gp130-binding site is removed from IL-6 and replaced with the LIF-receptor-binding site from CNTF, fused with the Fc domain of immunoglobulin G, creating a cytokine with CNTF-like, but IL-6-receptor-dependent, signalling. Here we show that IC7Fc improves glucose tolerance and hyperglycaemia and prevents weight gain and liver steatosis in mice. In addition, IC7Fc either increases, or prevents the loss of, skeletal muscle mass by activation of the transcriptional regulator YAP1. In human-cell-based assays, and in non-human primates, IC7Fc treatment results in no signs of inflammation or immunogenicity. Thus, IC7Fc is a realistic next-generation biological agent for the treatment of type 2 diabetes and muscle atrophy, disorders that are currently pandemic.

Suggested Citation

  • Maria Findeisen & Tamara L. Allen & Darren C. Henstridge & Helene Kammoun & Amanda E. Brandon & Laurie L. Baggio & Kevin I. Watt & Martin Pal & Lena Cron & Emma Estevez & Christine Yang & Greg M. Kowa, 2019. "Treatment of type 2 diabetes with the designer cytokine IC7Fc," Nature, Nature, vol. 574(7776), pages 63-68, October.
    • Handle: RePEc:nat:nature:v:574:y:2019:i:7776:d:10.1038_s41586-019-1601-9
    DOI: 10.1038/s41586-019-1601-9
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