Researchers have shown that, in contrast with what is observed in immortalized cell lines, CK2 expression and activity is not specifically impaired in F508delCFTR patients. In addition, they have analyzed the contribution of CK2 targeting in combination with different type of correctors or proteostasis regulator in our CK2 knockout cell models obtaining only modest results despite an overall reduction of HSP27 expression. On the contrary, HSP27 knockout CFBE cells show an improved response to correctors treatments leading to a strong functional recovery of F508delCFTR. Whilst, on the one hand, these pre-clinical studies minimize the effectiveness of CK2 as a potential target in treating F508delCFTR patients, on the other hand, they provide experimental evidence that HSP27 targeting could be a valuable strategy in a combinatory therapy with Vertex compounds.

Publications

Borgo C, Vilardell J, Bosello-Travain V et al. “Dependence of HSP27 cellular level on protein kinase CK2 discloses novel therapeutic strategies”, Biochim Biophys Acta Gen Subj. 2018 Dec;1862(12):2902-2910. doi: 10.1016/j.bbagen.2018.09.014. Epub 2018 Sep 20.