Elexacaftor–Tezacaftor–Ivacaftor Therapy for Cystic Fibrosis Patients with The F508del/Unknown Genotype
Marika Comegna,
Vito Terlizzi,
Donatello Salvatore,
Carmela Colangelo,
Antonella Miriam Di Lullo,
Immacolata Zollo,
Giovanni Taccetti,
Giuseppe Castaldo,
Felice Amato
Affiliations
Marika Comegna
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via Pansini, 5, 80131 Naples, Italy
Vito Terlizzi
Cystic Fibrosis Regional Reference Center, Department of Pediatric Medicine, Anna Meyer Children’s University, Viale Pieraccini, 24, 50139 Florence, Italy
Donatello Salvatore
Cystic Fibrosis Center, Hospital San Carlo, Via P. Petrone, 85100 Potenza, Italy
Carmela Colangelo
Cystic Fibrosis Center, Hospital San Carlo, Via P. Petrone, 85100 Potenza, Italy
Antonella Miriam Di Lullo
Department Reproductive Sciences and Dentistry, University of Naples Federico II of Neuroscience, Via Pansini, 5, 80131 Naples, Italy
Immacolata Zollo
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via Pansini, 5, 80131 Naples, Italy
Giovanni Taccetti
Cystic Fibrosis Regional Reference Center, Department of Pediatric Medicine, Anna Meyer Children’s University, Viale Pieraccini, 24, 50139 Florence, Italy
Giuseppe Castaldo
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via Pansini, 5, 80131 Naples, Italy
Felice Amato
Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via Pansini, 5, 80131 Naples, Italy
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.
