Treatment of type 2 diabetes with the designer cytokine IC7Fc
Details
Publication Year 2019-10, Volume 574, Issue #7776, Page 63-68
Journal Title
Nature
Publication Type
Journal Article
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.
Publisher
NPG
WEHI Research Division(s)
Blood Cells And Blood Cancer
PubMed ID
31554967
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2020-01-21 11:05:29
Last Modified: 2020-02-10 05:20:08
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