澳大利亚加文医学研究所Mark A. Febbraio研究团队利用人工设计的细胞因子IC7Fc对2型糖尿病进行治疗。这一研究成果2019年9月25日在线发表于国际学术期刊《自然》。
研究人员设计了gp130配体IC7Fc，其中一个gp130结合位点已从IL-6中移除，并被CNTF的LIF受体结合位点所取代，并与免疫球蛋白G的Fc结构域融合，从而创造了一个具有CNTF模样，但具有IL-6受体依赖性信号转导的细胞因子。研究人员IC7Fc可改善小鼠的葡萄糖耐量和高血糖症，并防止体重增加和肝脂肪变性。此外，IC7Fc通过激活转录调节因子YAP1来增加骨骼肌质量或防止其丢失。
基于人类细胞中的测试，以及在非人灵长类动物中的实验，IC7Fc治疗均未导致炎症或免疫原性迹象。因此，IC7Fc是用于治疗2型糖尿病和肌肉萎缩症（目前是大流行疾病）的一种实际的下一代生物制剂。
据介绍，gp130受体的细胞因子IL-6和CNTF可改善代谢稳态，但在治疗2型糖尿病方面的治疗用途有限。
附：英文原文
Title: Treatment of type 2 diabetes with the designer cytokine IC7Fc
Author: 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. Kowalski, Liam OReilly, Casey Egan, Emily Sun, Le May Thai, Guy Krippner, Timothy E. Adams, Robert S. Lee, Joachim Grtzinger, Christoph Garbers, Steve Risis
Issue&Volume: 2019-09-25
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.
DOI: 10.1038/s41586-019-1601-9
Source:https://www.nature.com/articles/s41586-019-1601-9
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
