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Efficacy of PEGylated ciliary neurotrophic factor superagonist variant in diet-induced obesity mice

Effect on body weight and food intake of short term administration of DH-CNTF and PEG-DH-CNTF in DIO mice
Effect on body weight and food intake of short term administration of DH-CNTF and PEG-DH-CNTF in DIO mice
Effect on body weight and food intake of short-term administration of DH-CNTF and PEG-DH-CNTF in DIO mice

At IRBM, we are passionate about understanding the underlying biology of disease, to drive drugdiscovery. In a recent paper funded by our consortium partner CNCCS, we evaluated the efficacy of a PEGylated Ciliary Neurotrophic Factor (CNTF) super-agonist variant in diet-induced obese mice.

CNTF is a neurotrophic cytokine able to induce appetite reduction, weight loss and antidiabetic effects. However, its susceptibility to neutralizing anti-CNTF antibodies in patients limits its use as a treatment for diabetes and obesity. In this published work, we describe the selection of DH-CNTF, a CNTF super agonist which has a 40-fold higher affinity for CNTF receptor α, as a candidate for PEGylation and evaluation in mouse PK and efficacy studies. We show that the PEGylated DH-CNTF analog provides improved half-life, enhanced weight loss effects and metabolic profile versus the unmodified protein indicating additional studies are warranted to understand its potential use as a weight reducing agent.

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