RT Journal Article
SR Electronic
T1 Asprosin Neutralizing Antibodies as a Treatment for Metabolic Syndrome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.15.298489
DO 10.1101/2020.09.15.298489
A1 Ila Mishra
A1 Clemens Duerrschmid
A1 Zhiqiang Ku
A1 Wei Xie
A1 Elizabeth Sabath Silva
A1 Jennifer Hoffmann
A1 Wei Xin
A1 Ningyan Zhang
A1 Zhiqiang An
A1 Atul R. Chopra
YR 2020
UL http://biorxiv.org/content/early/2020/10/04/2020.09.15.298489.abstract
AB Recently, we discovered a new glucogenic and centrally-acting orexigenic hormone – asprosin. Asprosin is elevated in metabolic syndrome (MS) patients, and importantly, its genetic loss results in reduced appetite, leanness and robust insulin sensitivity, leading to protection from MS. Here we demonstrate that anti-asprosin monoclonal antibodies (mAbs) are a dual-effect pharmacologic therapy that targets the two key pillars of MS – over-nutrition and the blood glucose burden. Anti-asprosin mAbs from three distinct species lowered appetite and body weight, and improved blood glucose in a dose-dependent and epitope-agnostic fashion in three independent MS mouse models, with an IC50 of ∼1.5 mg/kg. In addition, mAb treatment ameliorated MS associated dyslipidemia and hepatic dysfunction. The mAbs displayed half-life of over 3 days in vivo, with equilibrium dissociation-constants in picomolar to low nanomolar range. This evidence paves the way for further development towards an investigational new drug application and subsequent human trials for treatment of MS, a defining physical ailment of our time.Competing Interest StatementCompeting Financial interests A.R.C. is a cofounder and director of Vizigen, Inc.