Figure 1

Proof-of-concept studies in mice: effects of treatment on CFTR function in Cftr^{F508del/F508del}, CftrF508del^/−, Cftr^−/− and Cftr^{F508del/F508del}Becn1^+/– mice. Effects on CFTR function of oral administration of different combinations of cysteamine and EGCG in Cftr^{F508del/F508del} (a and d), Cftr^F508del/− (b and e) and Cftr^−/− (c and f) mice. The different treatment schedules are indicated. (a–c) Rectal potential difference (RPD) in vivo in response to 20 μM forskolin (Fsk) (mean±S.D.); (d–f) CFTR-dependent Cl⁻ secretion measured by means of forskolin-induced increase of the chloride current (I_sc (μA/cm²)) ex vivo in the ileum mounted in Ussing chambers and effects of CFTR inhibition (CFTR_inh-172, abbreviated Inh) and amiloride (abbreviated Am) for each group of treatment (#P<0.001 versus vehicle-treated mice). (g–i) Effects of treatment on CFTR function in Cftr^+/+Becn1^+/– (g), FVB/129Cftr^+/+ (h) and Cftr^{F508del/F508del}Becn1^+/– (i) mice. The different treatment schedules are indicated. CFTR-dependent Cl⁻ secretion measured as by means of forskolin-induced increase of the chloride current (I_sc (μA/cm²)) ex vivo in the ileum mounted in Ussing chambers and effects of CFTR inhibition (CFTR_inh-172, abbreviated Inh) and amiloride (abbreviated Am) for each group of treatment (^#P<0.001 versus vehicle-treated mice). Eight-week-old mice, n=10 per group of treatment. Treatments: Cys, cysteamine; EGCG, epigallocatechin gallate; Cys+EGCG, 5 days treatment with cysteamine and EGCG; Cys+Wo+EGCG, 5 days treatment with cysteamine and EGCG followed by 2 weeks of cysteamine washout in the presence of EGCG