Comegna Marika, Terlizzi Vito, Salvatore Donatello, Colangelo Carmela, Di Lullo Antonella Miriam, Zollo Immacolata, Taccetti Giovanni, Castaldo Giuseppe, Amato Felice
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via Pansini, 5, 80131 Naples, Italy.
CEINGE-Advanced Biotechnologies, Via G. Salvatore, 486, 80145 Naples, Italy.
Antibiotics (Basel). 2021 Jul 7;10(7):828. doi: 10.3390/antibiotics10070828.
The new CFTR modulator combination, elexacaftor/tezacaftor/ivacaftor (Trikafta) was approved by the FDA in October 2019 for treatment of Cystic Fibrosis in patients 6 years of age or older who have at least one F508del mutation in one allele and a minimal-function or another F508del mutation in the other allele. However, there is a group of patients, in addition to those with rare mutations, in which despite the presence of a F508del in one allele, it was not possible to identify any mutation in the other allele. To date, these patients are excluded from treatment with Trikafta in Italy, where the CF patients carrying F508del/unknown represent about 1.3% (71 patients) of the overall Italian CF patients. In this paper we show that the Trikafta treatment of nasal epithelial cells, derived from F508del/Unknown patients, results in a significant rescue of CFTR activity. Based on our findings, we think that the F508del/Unknown patients considered in this study could obtain clinical benefits from Trikafta treatment, and we strongly suggest their eligibility for this type of treatment. This study, adding further evidence in the literature, once again confirms the validity of functional studies on nasal cells in the cystic fibrosis theratyping and personalized medicine.
新型CFTR调节剂组合elexacaftor/tezacaftor/ivacaftor（Trikafta）于2019年10月获美国食品药品监督管理局（FDA）批准，用于治疗6岁及以上的囊性纤维化患者，这些患者的一个等位基因中至少有一个F508del突变，且另一个等位基因为最小功能突变或另一个F508del突变。然而，除了那些有罕见突变的患者外，还有一组患者，尽管其中一个等位基因存在F508del，但无法在另一个等位基因中鉴定出任何突变。迄今为止，在意大利，这些患者被排除在Trikafta治疗之外，在意大利，携带F508del/未知突变的囊性纤维化患者约占意大利囊性纤维化患者总数的1.3%（71例患者）。在本文中，我们表明，对来自F508del/未知患者的鼻上皮细胞进行Trikafta治疗，可显著挽救CFTR活性。基于我们的研究结果，我们认为本研究中所考虑的F508del/未知患者可能从Trikafta治疗中获得临床益处，我们强烈建议他们符合这种治疗类型的条件。这项研究在文献中增加了进一步的证据，再次证实了在囊性纤维化分型和个性化医疗中对鼻细胞进行功能研究的有效性。
