Emerging medicines to improve the basic defect in cystic fibrosis

References

• Riordan JR, Rommens JM, Kerem B, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989;245:1066–1073.
   PubMed Web of Science ®Google Scholar
• Bell SC, Mall MA, Gutierrez H, et al. The future of cystic fibrosis care: a global perspective. Lancet Respir Med. 2020;8:65–124.
   PubMed Web of Science ®Google Scholar
• Sheppard DN, Welsh MJ. Structure and function of the CFTR chloride channel. Physiol Rev. 1999;79:S23–45.
   PubMedGoogle Scholar
• Elborn JS. Cystic fibrosis. Lancet. 2016;388:2519–2531.
   PubMed Web of Science ®Google Scholar
• Castellani C, Duff AJA, Bell SC, et al. ECFS best practice guidelines: the 2018 revision. J Cyst Fibros. 2018;17:153–178.
   PubMed Web of Science ®Google Scholar
• US Cystic fibrosis registry (Cystic Fibrosis Foundation) annual data report 2020. [cited 2022 Apr 6]. Available from: https://www.cff.org/medical-professionals/patient-registry.
   Google Scholar
• Burgel P-R, Bellis G, Olesen HV, et al. Future trends in cystic fibrosis demography in 34 European countries. Eur Respir J. 2015;46:133–141.
   PubMed Web of Science ®Google Scholar
• Hanssens LS, Duchateau J, Casimir GJ. CFTR protein: not just a chloride channel? Cells. 2021;10:2844.
   PubMedGoogle Scholar
• Sosnay PR, Siklosi KR, Van Goor F, et al. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet. 2013;45:1160–1167.
   PubMed Web of Science ®Google Scholar
• Van Goor F, Hadida S, Grootenhuis PDJ, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A. 2009;106:18825–18830.
   PubMed Web of Science ®Google Scholar
• Eckford PDW, Li C, Ramjeesingh M, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator VX-770 (ivacaftor) opens the defective channel gate of mutant CFTR in a phosphorylation-dependent but ATP-independent manner. J Biol Chem. 2012;287:36639–36649.
   PubMed Web of Science ®Google Scholar
• Van Goor F, Yu H, Burton B, et al. Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. J Cyst Fibros. 2014;13:29–36.
   PubMed Web of Science ®Google Scholar
• Accurso FJ, Rowe SM, Clancy JP, et al. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med. 2010;363:1991–2003.
   PubMed Web of Science ®Google Scholar
• Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365:1663–1672.
   PubMed Web of Science ®Google Scholar
• De Boeck K, Munck A, Walker S, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. J Cyst Fibros. 2014;13:674–680.
   PubMed Web of Science ®Google Scholar
• Davies JC, Cunningham S, Harris WT, et al. Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. Lancet Respir Med. 2016;4:107–115.
   PubMed Web of Science ®Google Scholar
• Rosenfeld M, Wainwright CE, Higgins M, et al. Ivacaftor treatment of cystic fibrosis in children aged 12 to <24 months and with a CFTR gating mutation (ARRIVAL): a phase 3 single-arm study. Lancet Respir Med. 2018;6:545–553.
   PubMed Web of Science ®Google Scholar
• Durmowicz AG, Lim R, Rogers H, et al. The U.S. food and drug administration’s experience with ivacaftor in cystic fibrosis. Establishing efficacy using in vitro data in Lieu of a clinical trial. Ann Am Thorac Soc. 2018;15:1–2.
   PubMed Web of Science ®Google Scholar
• Volkova N, Moy K, Evans J, et al. Disease progression in patients with cystic fibrosis treated with ivacaftor: data from national US and UK registries. J Cyst Fibros. 2020;19:68–79.
   PubMed Web of Science ®Google Scholar
• Accurso FJ, Van Goor F, Zha J, et al. Sweat chloride as a biomarker of CFTR activity: proof of concept and ivacaftor clinical trial data. J Cyst Fibros. 2014;13:139–147.
   PubMed Web of Science ®Google Scholar
• Abdallah K, De Boeck K, Dooms M, et al. A comparative analysis of pricing and reimbursement of cystic fibrosis transmembrane conductance regulator modulators in Europe. Front Pharmacol. 2021;12:746710.
   PubMedGoogle Scholar
• Flume PA, Liou TG, Borowitz DS, et al. Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation. Chest. 2012;142:718–724.
   PubMed Web of Science ®Google Scholar
• Ren HY, Grove DE, De La Rosa O, et al. VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1. Mol Biol Cell. 2013;24:3016–3024.
   PubMed Web of Science ®Google Scholar
• Van Goor F, Hadida S, Grootenhuis PDJ, et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A. 2011;108:18843–18848.
   PubMed Web of Science ®Google Scholar
• Boyle MP, Bell SC, Konstan MW, et al. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med. 2014;2:527–538.
   PubMed Web of Science ®Google Scholar
• Wainwright CE, Elborn JS, Ramsey BW, et al. Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med. 2015;373:220–231.
   PubMed Web of Science ®Google Scholar
• Taylor-Cousar JL, Munck A, McKone EF, et al. Tezacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del. N Engl J Med. 2017;377:2013–2023.
   PubMed Web of Science ®Google Scholar
• Keating D, Marigowda G, Burr L, et al. VX-445-tezacaftor-ivacaftor in patients with cystic fibrosis and one or two Phe508del Alleles. N Engl J Med. 2018;379:1612–1620.
   PubMed Web of Science ®Google Scholar
• Middleton PG, Mall MA, Dřevínek P, et al. Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med. 2019;381:1809–1819.
   PubMed Web of Science ®Google Scholar
• Nichols DP, Paynter AC, and Heltshe SL, et al. Clinical effectiveness of elexacaftor/tezacftor/ivacaftor in people with cystic fibrosis. Am J Respir Crit Care Med. 2022;205:529–39.
   PubMed Web of Science ®Google Scholar
• Burgel P-R, Durieu I, Chiron R, et al. Rapid improvement after starting elexacaftor-tezacaftor-ivacaftor in patients with cystic fibrosis and advanced pulmonary disease. Am J Respir Crit Care Med. 2021;204:64–73.
   PubMedGoogle Scholar
• Flume PA, Sawicki GS, Pressler T, et al. Phase 2 initial results evaluating PTI-428, a novel CFTR amplifier, in patients with cystic fibrosis. J Cyst Fibros. 2018;17S(3):S1.
   Google Scholar
• Vu A, McCray PB. New directions in pulmonary gene therapy. Hum Gene Ther. 2020;31:921–939.
   PubMedGoogle Scholar
• Cooney A, McCray P, Sinn P. Cystic fibrosis gene therapy: looking back, looking forward. Genes (Basel). 2018;9:538.
   Web of Science ®Google Scholar
• Alton EWFW, Beekman JM, Boyd AC, et al. Preparation for a first-in-man lentivirus trial in patients with cystic fibrosis. Thorax. 2017;72:137–147.
   PubMed Web of Science ®Google Scholar
• Excoffon K, Smith M, Lin S, et al. Delivery of SP-101 restores CFTR function in human CF airway epithelial cultures and drives hCFTRΔR transgene expression in the airways of ferrets. J Cyst Fibros. 2021;20S2:S278.
   Google Scholar
• Allan KM, Farrow N, Donnelley M, et al. Treatment of cystic fibrosis: from gene- to cell-based therapies. Front Pharmacol. 2021;12:639475.
   PubMedGoogle Scholar
• Rollet-Cohen V, Bourderioux M, Lipecka J, et al. Comparative proteomics of respiratory exosomes in cystic fibrosis, primary ciliary dyskinesia and asthma. J Proteomics. 2018;185:1–7.
   PubMedGoogle Scholar
• Villamizar O, Waters SA, Scott T, et al. Mesenchymal stem cell exosome delivered zinc finger protein activation of cystic fibrosis transmembrane conductance regulator. J Extracell Vesicles. 2021;10:e12053.
   PubMedGoogle Scholar
• Joshi D, Ehrhardt A, Hong JS, et al. Cystic fibrosis precision therapeutics: emerging considerations. Pediatr Pulmonol. 2019;54(Suppl 3):S13–S17.
   PubMedGoogle Scholar
• Boyd AC, Guo S, Huang L, et al. New approaches to genetic therapies for cystic fibrosis. J Cyst Fibros. 2020;19:S54–S59.
   PubMedGoogle Scholar
• Hodges CA, Conlon RA. Delivering on the promise of gene editing for cystic fibrosis. Genes Dis. 2019;6:97–108.
   PubMedGoogle Scholar
• Schwank G, Koo B-K, Sasselli V, et al. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell. 2013;13:653–658.
   PubMed Web of Science ®Google Scholar
• Ruan J, Hirai H, Yang D, et al. Efficient gene editing at major CFTR mutation loci. Mol Ther Nucleic Acids. 2019;16:73–81.
   PubMedGoogle Scholar
• Ernst MPT, Broeders M, Herrero-Hernandez P, et al. Ready for repair? Gene editing enters the clinic for the treatment of human disease. Mol Ther Methods Clin Dev. 2020;18:532–557.
   PubMedGoogle Scholar
• Hajj KA, Whitehead KA. Tools for translation: non-viral materials for therapeutic mRNA delivery. Nat Rev Mater. 2017;2:17056.
   Web of Science ®Google Scholar
• Kuhn AN, Beiβert T, Simon P, et al. mRNA as a versatile tool for exogenous protein expression. Curr Gene Ther. 2012;12:347–361.
   PubMedGoogle Scholar
• Ward CL, Kopito RR. Intracellular turnover of cystic fibrosis transmembrane conductance regulator. Inefficient processing and rapid degradation of wild-type and mutant proteins. J Biol Chem. 1994;269:25710–25718.
   PubMed Web of Science ®Google Scholar
• Robinson E, MacDonald KD, Slaughter K, et al. Lipid nanoparticle-delivered chemically modified mRNA restores chloride secretion in cystic fibrosis. Mol Ther. 2018;26:2034–2046.
   PubMed Web of Science ®Google Scholar
• Haque AKMA, Dewerth A, Antony JS, et al. Chemically modified hCFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis. Sci Rep. 2018;8:16776.
   PubMedGoogle Scholar
• Ramalho AS, Beck S, Meyer M, et al. Five percent of normal cystic fibrosis transmembrane conductance regulator mRNA ameliorates the severity of pulmonary disease in cystic fibrosis. Am J Respir Cell Mol Biol. 2002;27:619–627.
   PubMed Web of Science ®Google Scholar
• Porter JJ, Heil CS, Lueck JD. Therapeutic promise of engineered nonsense suppressor tRNAs. WIREs RNA. 2021;12. DOI:10.1002/wrna.1641.
   Google Scholar
• Lueck JD, Yoon JS, Perales-Puchalt A, et al. Engineered transfer RNAs for suppression of premature termination codons. Nat Commun. 2019;10:822.
   PubMedGoogle Scholar
• Levin AA. Treating disease at the RNA level with oligonucleotides. N Engl J Med. 2019;380:57–70.
   PubMed Web of Science ®Google Scholar
• Beumer W, Swildens J, Leal T, et al. Evaluation of eluforsen, a novel RNA oligonucleotide for restoration of CFTR function in in vitro and murine models of p.Phe508del cystic fibrosis. PLOS ONE. 2019;14:e0219182.
   PubMedGoogle Scholar
• Sermet-Gaudelus I, Clancy JP, Nichols DP, et al. Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis. J Cyst Fibros. 2019;18:536–542.
   PubMedGoogle Scholar
• Drevinek P, Pressler T, Cipolli M, et al. Antisense oligonucleotide eluforsen is safe and improves respiratory symptoms in F508del cystic fibrosis. J Cyst Fibros. 2020;19:99–107.
   PubMedGoogle Scholar
• Faustino NA. Pre-mRNA splicing and human disease. Genes Dev. 2003;17:419–437.
   PubMed Web of Science ®Google Scholar
• Nissim-Rafinia M, Kerem B. Splicing regulation as a potential genetic modifier. Trends Genet. 2002;18:123–127.
   PubMed Web of Science ®Google Scholar
• Igreja S, Clarke LA, Botelho HM, et al. Correction of a cystic fibrosis splicing mutation by antisense oligonucleotides. Hum Mutat. 2016;37:209–215.
   PubMed Web of Science ®Google Scholar
• Michaels WE, Bridges RJ, Hastings ML. Antisense oligonucleotide-mediated correction of CFTR splicing improves chloride secretion in cystic fibrosis patient-derived bronchial epithelial cells. Nucleic Acids Res. 2020;48:7454–7467.
   PubMed Web of Science ®Google Scholar
• Mort M, Ivanov D, Cooper DN, et al. A meta-analysis of nonsense mutations causing human genetic disease. Hum Mutat. 2008;29:1037–1047.
   PubMed Web of Science ®Google Scholar
• Mendell JT, Dietz HC. When the message goes awry. Cell. 2001;107:411–414.
   PubMed Web of Science ®Google Scholar
• Frischmeyer PA. Nonsense-mediated mRNA decayin health and disease. Hum Mol Genet. 1999;8(10):1893–1900.
   PubMed Web of Science ®Google Scholar
• McCague AF, Raraigh KS, Pellicore MJ, et al. Correlating cystic fibrosis transmembrane conductance regulator function with clinical features to inform precision treatment of cystic fibrosis. Am J Respir Crit Care Med. 2019;199:1116–1126.
   PubMed Web of Science ®Google Scholar
• Howard M, Frizzell RA, Bedwell DM. Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations. Nat Med. 1996;2:467–469.
   PubMed Web of Science ®Google Scholar
• Sermet-Gaudelus I, Renouil M, Fajac A, et al. In vitro prediction of stop-codon suppression by intravenous gentamicin in patients with cystic fibrosis: a pilot study. BMC Med. 2007;5:5.
   PubMed Web of Science ®Google Scholar
• Wilschanski M, Yahav Y, Yaacov Y, et al. Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations. N Engl J Med. 2003;349:1433–1441.
   PubMed Web of Science ®Google Scholar
• Kerem E, Konstan MW, De Boeck K, et al. Ataluren for the treatment of nonsense-mutation cystic fibrosis: a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Respir Med. 2014;2:539–547.
   PubMed Web of Science ®Google Scholar
• Crawford DK, Mullenders J, Pott J, et al. Targeting G542X CFTR nonsense alleles with ELX-02 restores CFTR function in human-derived intestinal organoids. J Cyst Fibros. 2021;20:436–442.
   PubMed Web of Science ®Google Scholar
• de Poel E, Spelier S, and Suen SWF, et al. Functional restoration of cftr nonsense mutations in intestinal organoids. J Cyst Fibros. 2022;21:246–253.
   PubMedGoogle Scholar
• Floquet C, Hatin I, Rousset J-P, et al. Statistical analysis of readthrough levels for nonsense mutations in mammalian cells reveals a major determinant of response to gentamicin. PLoS Genet. 2012;8:e1002608.
   PubMed Web of Science ®Google Scholar
• Keenan MM, Huang L, Jordan NJ, et al. Nonsense-mediated RNA decay pathway Inhibition restores expression and function of W1282X CFTR. Am J Respir Cell Mol Biol. 2019;61:290–300.
   PubMedGoogle Scholar
• Pranke I, Bidou L, and Martin N, et al. Factors influencing readthrough therapy for frequent cystic fibrosis premature termination codons. ERJ Open Res. 2018;4:00080–2017.
   PubMedGoogle Scholar
• Huang SXL, Green MD, de Carvalho AT, et al. The in vitro generation of lung and airway progenitor cells from human pluripotent stem cells. Nat Protoc. 2015;10:413–425.
   PubMed Web of Science ®Google Scholar
• Hawkins FJ, Suzuki S, Beermann ML, et al. Derivation of airway basal stem cells from human pluripotent stem cells. Cell Stem Cell. 2021;28:79–95.e8.
   PubMedGoogle Scholar
• Crane AM, Kramer P, Bui JH, et al. Targeted correction and restored function of the CFTR gene in cystic fibrosis induced pluripotent stem cells. Stem Cell Rep. 2015;4:569–577.
   PubMed Web of Science ®Google Scholar
• Berical A, Lee RE, Randell SH, et al. Challenges facing airway epithelial cell-based therapy for cystic fibrosis. Front Pharmacol. 2019;10:74.
   PubMed Web of Science ®Google Scholar
• Hayes D, Kopp BT, Hill CL, et al. Cell therapy for cystic fibrosis lung disease: regenerative basal cell amplification. Stem Cells Transl Med. 2019;8:225–235.
   PubMedGoogle Scholar