The project included murine and human studies: in vitro, to assess the effect of Anakinra on expression, cellular localization and functional activity of p.Phe508del-CFTR and the molecular mechanisms behind Anakinra’s rescuing activity in p.Phe508del-CFTR-transfected CFBE41o-cells and HBE cells from patients homozygous for the p.Phe508del-CFTR mutation and controls; in vivo, in CftrF508del mice to define the pharmacology of Anakinra. The results have indicated that anakinra is able to exert CFTR rescuing activity in p.Phe508del-CFTR-transfected CFBE41o- cells and HBE cells from CF patients, through both the conventional and unconventional secretion pathways. Studies are underway to define the possible molecular mechanisms underlying the ability of Anakinra to promote both pathways. Ultimately, the ongoing studies on the comparative activity of Anakinra alone or combined with correctors and/or potentiators on chloride channel activity are definitely required to validate the repurposing of Anakinra as a therapeutic agent in CF.

 Pubblications

– Piliponsky AM, Romani L “The contribution of mast cells to bacterial and fungal infection immunity” Immunol Rev. 282:188-197, 2018.
– Pariano M et all. “Anakinra rescues p.Phe508del-CFTR protein via conventional and unconventional secretory pathways”. Manuscript in preparation