Treatment of Cystic Fibrosis Patients Homozygous for <i>F508del</i> with Lumacaftor-Ivacaftor (Orkambi<sup>®</sup>) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells
The treatment of cystic fibrosis (CF) patients homozygous for the <i>F508del</i> mutation with Orkambi<sup>®</sup>, a combination of a corrector (lumacaftor) and a potentiator (ivacaftor) of the mutated CFTR protein, resulted in some amelioration of the respiratory function....
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| Format: | Article |
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MDPI AG
2020-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/7/2398 |
| _version_ | 1797571857556176896 |
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| author | Maria Favia Crescenzio Gallo Lorenzo Guerra Domenica De Venuto Anna Diana Angela Maria Polizzi Pasqualina Montemurro Maria Addolorata Mariggiò Giuseppina Leonetti Antonio Manca Valeria Casavola Massimo Conese |
| author_facet | Maria Favia Crescenzio Gallo Lorenzo Guerra Domenica De Venuto Anna Diana Angela Maria Polizzi Pasqualina Montemurro Maria Addolorata Mariggiò Giuseppina Leonetti Antonio Manca Valeria Casavola Massimo Conese |
| author_sort | Maria Favia |
| collection | DOAJ |
| description | The treatment of cystic fibrosis (CF) patients homozygous for the <i>F508del</i> mutation with Orkambi<sup>®</sup>, a combination of a corrector (lumacaftor) and a potentiator (ivacaftor) of the mutated CFTR protein, resulted in some amelioration of the respiratory function. However, a great variability in the clinical response was also observed. The aim of this study was to evaluate the response to Orkambi<sup>®</sup> in a small cohort of F508del/F508del patients (<i>n</i> = 14) in terms of clinical and laboratory parameters, including ex vivo CFTR activity in mononuclear cells (MNCs), during a 12-month treatment. Patients responded with an increase in percent predicted forced expiratory volume in 1 s (FEV<sub>1</sub>%) and body mass index (BMI) as well as with a decrease in white blood cell (WBC) total counts and serum C-reactive protein (CRP) levels, although not significantly. Sweat chloride and CFTR-dependent chloride efflux were found to decrease and increase, respectively, as compared with pre-therapy values. CFTR and BMI showed a statistically significant correlation during Orkambi<sup>®</sup> treatment. Clustering analysis showed that CFTR, BMI, sweat chloride, FEV<sub>1</sub>%, and WBC were strongly associated. These data support the notion that CFTR-dependent chloride efflux in MNCs should be investigated as a sensitive outcome measure of Orkambi<sup>®</sup> treatment in CF patients. |
| first_indexed | 2024-03-10T20:46:37Z |
| format | Article |
| id | doaj.art-2af28fec6b1140a1aa13818cfa80e423 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:46:37Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2af28fec6b1140a1aa13818cfa80e4232023-11-19T20:12:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-03-01217239810.3390/ijms21072398Treatment of Cystic Fibrosis Patients Homozygous for <i>F508del</i> with Lumacaftor-Ivacaftor (Orkambi<sup>®</sup>) Restores Defective CFTR Channel Function in Circulating Mononuclear CellsMaria Favia0Crescenzio Gallo1Lorenzo Guerra2Domenica De Venuto3Anna Diana4Angela Maria Polizzi5Pasqualina Montemurro6Maria Addolorata Mariggiò7Giuseppina Leonetti8Antonio Manca9Valeria Casavola10Massimo Conese11Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyCystic Fibrosis Regional Center, Department of Biomedical and Human Oncology, Pediatrics Section, U.O. “B. Trambusti”, Policlinico, University of Bari, 70124 Bari, ItalyUOC Laboratorio di Genetica Medica, Department of Biomedical and Human Oncology, Policlinico, University of Bari, 70124 Bari, ItalyUOC Laboratorio di Genetica Medica, Department of Biomedical and Human Oncology, Policlinico, University of Bari, 70124 Bari, ItalyDepartment of Biomedical Sciences and Human Oncology, Section of General Pathology, University of Bari, 70124 Bari, ItalyDepartment of Biomedical Sciences and Human Oncology, Section of General Pathology, University of Bari, 70124 Bari, ItalyCystic Fibrosis Regional Center, Department of Biomedical and Human Oncology, Pediatrics Section, U.O. “B. Trambusti”, Policlinico, University of Bari, 70124 Bari, ItalyCystic Fibrosis Regional Center, Department of Biomedical and Human Oncology, Pediatrics Section, U.O. “B. Trambusti”, Policlinico, University of Bari, 70124 Bari, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, ItalyThe treatment of cystic fibrosis (CF) patients homozygous for the <i>F508del</i> mutation with Orkambi<sup>®</sup>, a combination of a corrector (lumacaftor) and a potentiator (ivacaftor) of the mutated CFTR protein, resulted in some amelioration of the respiratory function. However, a great variability in the clinical response was also observed. The aim of this study was to evaluate the response to Orkambi<sup>®</sup> in a small cohort of F508del/F508del patients (<i>n</i> = 14) in terms of clinical and laboratory parameters, including ex vivo CFTR activity in mononuclear cells (MNCs), during a 12-month treatment. Patients responded with an increase in percent predicted forced expiratory volume in 1 s (FEV<sub>1</sub>%) and body mass index (BMI) as well as with a decrease in white blood cell (WBC) total counts and serum C-reactive protein (CRP) levels, although not significantly. Sweat chloride and CFTR-dependent chloride efflux were found to decrease and increase, respectively, as compared with pre-therapy values. CFTR and BMI showed a statistically significant correlation during Orkambi<sup>®</sup> treatment. Clustering analysis showed that CFTR, BMI, sweat chloride, FEV<sub>1</sub>%, and WBC were strongly associated. These data support the notion that CFTR-dependent chloride efflux in MNCs should be investigated as a sensitive outcome measure of Orkambi<sup>®</sup> treatment in CF patients.https://www.mdpi.com/1422-0067/21/7/2398cystic fibrosisOrkambi<sup>®</sup>CFTRmononuclear cellsBMIsweat chloride |
| spellingShingle | Maria Favia Crescenzio Gallo Lorenzo Guerra Domenica De Venuto Anna Diana Angela Maria Polizzi Pasqualina Montemurro Maria Addolorata Mariggiò Giuseppina Leonetti Antonio Manca Valeria Casavola Massimo Conese Treatment of Cystic Fibrosis Patients Homozygous for <i>F508del</i> with Lumacaftor-Ivacaftor (Orkambi<sup>®</sup>) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells International Journal of Molecular Sciences cystic fibrosis Orkambi<sup>®</sup> CFTR mononuclear cells BMI sweat chloride |
| title | Treatment of Cystic Fibrosis Patients Homozygous for <i>F508del</i> with Lumacaftor-Ivacaftor (Orkambi<sup>®</sup>) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells |
| title_full | Treatment of Cystic Fibrosis Patients Homozygous for <i>F508del</i> with Lumacaftor-Ivacaftor (Orkambi<sup>®</sup>) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells |
| title_fullStr | Treatment of Cystic Fibrosis Patients Homozygous for <i>F508del</i> with Lumacaftor-Ivacaftor (Orkambi<sup>®</sup>) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells |
| title_full_unstemmed | Treatment of Cystic Fibrosis Patients Homozygous for <i>F508del</i> with Lumacaftor-Ivacaftor (Orkambi<sup>®</sup>) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells |
| title_short | Treatment of Cystic Fibrosis Patients Homozygous for <i>F508del</i> with Lumacaftor-Ivacaftor (Orkambi<sup>®</sup>) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells |
| title_sort | treatment of cystic fibrosis patients homozygous for i f508del i with lumacaftor ivacaftor orkambi sup r sup restores defective cftr channel function in circulating mononuclear cells |
| topic | cystic fibrosis Orkambi<sup>®</sup> CFTR mononuclear cells BMI sweat chloride |
| url | https://www.mdpi.com/1422-0067/21/7/2398 |
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