A new therapeutic approach for type 1 diabetes: Rationale for GNbAC1, an anti-HERV-W-Env monoclonal antibody

Diabetes, Obesity & Metabolism
Francois CurtinRAINBOW-T1D investigators

Abstract

We describe a newly identified therapeutic target for type 1 diabetes (T1D): an envelope protein of endogenous retroviral origin, human endogenous retrovirus W envelope (HERV-W-Env). HERV-W-Env was found to be detected in the blood of ~60% of patients with T1D and is expressed in acinar pancreatic cells of 75% of patients with T1D at post mortem examination. Preclinical experiments showed that this protein displays direct cytotoxicity on human β-islet cells. In vivo HERV-W-Env impairs the insulin and glucose metabolism in transgenic mice expressing HERV-W-Env. GNbAC1, an IgG4 monoclonal antibody, has been developed to specifically target HERV-W-Env and to neutralize the effect of HERV-W-Env in vitro and in vivo. GNbAC1 is currently in clinical development for multiple sclerosis and > 300 subjects have been administered with GNbAC1 so far. GNbAC1 is now being tested in T1D in the RAINBOW-T1D study, which is a randomized placebo-controlled study with the objective of showing the safety and pharmacodynamic response of GNbAC1 in patients who have had T1D with a maximum of 4 years' duration. GNbAC1 is being tested vs placebo at the dose of 6 mg/kg in 60 patients during six repeated administrations for 6 months; a 6-month open-label ...Continue Reading

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Citations

Jan 8, 2019·Reviews in Medical Virology·Mengwen ZhangShu Zheng
Nov 23, 2019·Current Diabetes Reports·Sandrine LevetD Hober
Aug 15, 2020·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Gabrielle Kornmann, François Curtin
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Mar 25, 2019·Current Diabetes Reports·Griselda Lim Loo XinDinesh Kumar Chellappan
Jun 3, 2021·Pharmaceuticals·Karen Giménez-Orenga, Elisa Oltra

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