Modifying disease in cystic fibrosis: Current and future therapies on the horizon

Current Opinion in Pulmonary Medicine

Volumn 19, Issue 6, 2013, Pages 645-651

  Ong, Thida ^a   Ramsey, Bonnie W ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

airway surface liquid; cystic fibrosis; cystic fibrosis transmembrane conductance regulator protein modulator; gene therapy

Indexed keywords

ATALUREN; CHLORIDE CHANNEL STIMULATING AGENT; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DENUFOSOL; GENTAMICIN; IVACAFTOR; LUMACAFTOR; MANNITOL; N 6022; PLACEBO; SODIUM CHLORIDE; UNCLASSIFIED DRUG; VX 661;

CYSTIC FIBROSIS; DISEASE COURSE; DISEASE MARKER; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG POTENTIATION; DRUG SAFETY; EXPERIMENTAL THERAPY; FORCED EXPIRATORY VOLUME; GENE MUTATION; GENE REPLACEMENT THERAPY; HUMAN; LUNG FIBROSIS; MONOTHERAPY; NONHUMAN; NONSENSE MUTATION; OSMOSIS; PATHOPHYSIOLOGY; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); REVIEW; STEM CELL GENE THERAPY; TREATMENT RESPONSE;

AMINOPHENOLS; BIOLOGICAL MARKERS; CELL MEMBRANE; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; FEMALE; GENETIC MARKERS; GENETIC THERAPY; HUMANS; MALE; MANNITOL; MUTATION; PHENOTYPE; QUINOLONES; RESPIRATORY SYSTEM AGENTS; SALINE SOLUTION, HYPERTONIC;

EID: 84885183918     PISSN: 10705287     EISSN: 15316971     Source Type: Journal    
DOI: 10.1097/MCP.0b013e328365ab5f     Document Type: Review

References (71)

1. Rowe SM, Borowitz DS, Burns JL, et al. Progress in cystic fibrosis and the CF Therapeutics Development Network. Thorax 2012; 67:882-890.
2. Cystic Fibrosis Foundation. National Patient Registry Annual Data report. Bethesda, Maryland, USA; 2011.
3. Welsh MJ, Ramsey BW, Accurso F, Cutting GR. Cystiv fibrosis. In: Scriver CR, Beaudet AL, Valle D, Sly WS, editors. The metabolic and molecular bases of inherited diseases, 8th ed New York: McGraw-Hill; 2001. pp. 5121-5188.
4. North American Cystic Fibrosis Conference. Reversin. The basic defect\: A vision fo. The future. 2012. http://www.nacfconference.org/plen.archive.html. [Accessed on 5 April 2013]
5. Rowe SM, Miller S, Sorscher EJ. Cystic fibrosis. N Engl J Med 2005; 352:1992-2001.
6. Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science 1989; 245:1073-1080.
7. Prickett M, Jain M. Gene therapy in cystic fibrosis. Transl Res 2013; 161:255-264.
8. Alton EW, Boyd AC, Cheng SH, et al. A randomised, double-blind, placebocontrolled phase IIB clinical trial of repeated application of gene therapy in patients with cystic fibrosis. Thorax . doi:10.1136/thoraxjnl-2013- 203309. [Epub ahead of print]
9. Griesenbach U, Alton EW. Progress in gene and cell therapy for cystic fibrosis lung disease. Curr Pharm Des 2012; 18:642-662.
10. Griesenbach U, Alton EW. Expert opinion in biological therapy: update on developments in lung gene transfer. Expert Opin Biol Ther 2013; 13:345-360.
11. Griesenbach U, Inoue M, Meng C, et al. Assessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for lung gene therapy. Am J Respir Crit Care Med 2012; 186:846-856.
12. Potash AE, Wallen TJ, Karp PH, et al. Adenoviral gene transfer correct. The ion transport defect in the sinus epithelia of a porcine CF model. Mol Ther 2013; 21:947-953.
13. Paracchini V, Carbone A, Colombo F, et al. Amniotic mesenchymal stem cells\: A new source for hepatocyte-like cells and induction of CFTR expression by coculture with cystic fibrosis airway epithelial cells. J Biomed Biotechnol 2012; 2012:575471.
14. Ferec C, Cutting GR. Assessin. The disease-liability of mutations in CFTR. Cold Spring Harb Perspect Med 2012; 2:a009480.
15. Welsh MJ, Smith AE. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 1993; 73:1251-1254.
16. Sloane PA, Rowe SM. Cystic fibrosis transmembrane conductance regulator protein repair as a therapeutic strategy in cystic fibrosis. Curr Opin Pulm Med 2010; 16:591-597.
17. Rowntree RK, Harris A. The phenotypic consequences of CFTR mutations. Ann Hum Genet 2003; 67:471-485.
18. Johns Hopkins University (CFTR2 Team): Clinical and Functional Translation of CFTR (CFTR2). www.cftr2.org. [Accessed on 4 August 2013]
19. Zielenski J, Tsui LC. Cystic fibrosis: genotypic and phenotypic variations. Annu Rev Genet 1995; 29:777-807.
20. Haardt M, Benharouga M, Lechardeur D, et al. C-terminal truncations destabiliz. The cystic fibrosis transmembrane conductance regulator without impairing its biogenesis. A novel class of mutation. J Biol Chem 1999; 274: 21873-21877.
21. 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.
22. Davies JC, Wainwright CE, Canny GJ, et al. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med 2013; 187:1219-1225.
23. Mckone E, Li H, Gilmartin G, Davies JC. Long-term safety and efficacy of ivacaftor in persons with cystic fibrosis who hav. The G551D-CFTR mutation. Pediatr Pulmonol Suppl 2012; S35:296.
24. Flume PA, Liou TG, Borowitz DS, et al. Ivacaftor in subjects with cystic fibrosis who are homozygous fo. The F508del-CFTR mutation. Chest 2012; 142: 718-724.
25. Yu H, Burton B, Huang CJ, et al. Ivacaftor potentiation of multiple CFTR channels with gating mutations. J Cyst Fibros 2012; 11:237-245.
26. Van Goor F, Yu H, Burton B, et al. Ivacaftor potentiates mutant CFTR forms associated with residual CFTR function. J Cyst Fibros 2012; 11:S31.
27. Pilot Study Testin. The Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis and Residual CFTR Function. 2012. http://www. clinicaltrials. gov/ct2/show/nct01685801. [Accessed on 24 April 2013]
28. Study of Ivacaftor in Subjects With Cystic Fibrosis Who Have a Non-G551D CFTR Gating Mutation (KONNECTION). 2013. www.clinicaltrials.gov/ct2/show/ nct01614470. [Accessed on 2 May 2013]
29. Study of Ivacaftor in Subjects With Cystic Fibrosis Who Hav. The R117HCFTR Mutation (KONDUCT). 2013. http://www.clinicaltrials.gov/ct2/show/ nct01614457. [Accessed on 2 May 2013]
30. Van Goor F, Hadida S, Grootenhuis PD, et al. Correction of the F508del-CFTR protein processing defect in vitro b. The investigational drug VX-809. Proc Natl Acad Sci U S A 2011; 108:18843-18848.
31. Clancy JP, Rowe SM, Accurso FJ, et al. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous fo. The F508del-CFTR mutation. Thorax 2012; 67:12-18.
32. Vertex Pharmaceuticals Inc. Final data from phase 2 combination study of VX-809 and KALYDECO (ivacaftor) showed statistically significant improvement inlung function in people with cystic fibrosis who have two copies of the F508del mutation. http://investors.vrtx.com/releasedetail.cfm?ReleaseID= 687394. [Accessed on 5 April 2013]
33. Boyle MP, Bell S, Konstan M, et al. The investigational CFTR corrector, VX-809 (lumacaftor) co-administered wit. The oral potentiator ivacaftor improved CFTR and lung function in F508DEL homozygous patients: phase II study results. Pediatr Pulmonol Suppl 2012; S35:315.
34. A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous fo. The F508del-CFTR Mutation (TRANSPORT). 2013. http://clinicaltrials.gov/ct2/show/NCT01807949. [Accessed on 24 April 2013]
35. A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous fo. The F508del-CFTR Mutation (TRAFFIC). 2013. http://clinicaltrials.gov/ct2/show/NCT01807923. [Accessed on 24 April 2013]
36. Van Goor F, Straley KS, Cao D, et al. Rescue of DeltaF508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules. Am J Physiol Lung Cell Mol Physiol 2006; 290:L1117-1130.
37. Study of VX-661 Alone and in Combination With VX-770 in Subjects Homozygous to the F508del-CFTR Mutation. 2013. http://clinicaltrials.gov/ct2/ show/NCT01531673. [Accessed on 2 May 2013]
38. Treatment with VX-661 and Ivacaftor in a Phase 2 Study Resulted in Statistically Significant Improvements in Lung Function in People with Cystic Fibrosis Who Have Two Copies of the F508del Mutation. 2013. http://investors. vrtx.com/releasedetail.cfm?ReleaseID=757597. [Accessed on 29 May 2013]
39. Zaman K, Fraser-Butler M, Bennett D. Novel s-nitrosothiols have potential therapeutic uses for cystic fibrosis. Curr Pharm Des 2013; 19:3509-3520.
40. Green LS, Chun LE, Patton AK, et al. Mechanism of inhibition for N6022, a first-in-class drug targeting S-nitrosoglutathione reductase. Biochemistry 2012; 51:2157-2168.
41. Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous fo. The F508del-CFTR Mutation. April 22, 2013. http://clinicaltrials. gov/ct2/show/NCT01746784. [Accessed on 2 May 2013]
42. 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.
43. Clancy JP, Rowe SM, Bebok Z, et al. No detectable improvements in cystic fibrosis transmembrane conductance regulator by nasal aminoglycosides in patients with cystic fibrosis with stop mutations. Am J Respir Cell Mol Biol 2007; 37:57-66.
44. Du M, Liu X, Welch EM, et al. PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model. Proc Natl Acad Sci U S A 2008; 105:2064-2069.
45. Kerem E, Hirawat S, Armoni S, et al. Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations\: A prospective phase II trial. Lancet 2008; 372:719-727.
46. Sermet-Gaudelus I, Boeck KD, Casimir GJ, et al. Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis. Am J Respir Crit Care Med 2010; 182:1262-1272.
47. PTC Therapeutics I. http://ptct.client.shareholder.com/releasedetail.cfm? ReleaseID= 681445. [Accessed on 5 April 2013]
48. Mogayzel PJ Jr, Naureckas ET, Robinson KA, et al. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2013; 187:680-689.
49. Rosenfeld M, Ratjen F, Brumback L, et al. Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis. The ISIS randomized controlled trial. JAMA 2012; 307:2269-2277.
50. Bilton D, Robinson P, Cooper P, et al. Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study. Eur Respir J 2011; 38:1071-1080.
51. Aitken ML, Bellon G, De Boeck K, et al. Long-term inhaled dry powder mannitol in cystic fibrosis: an international randomized study. Am J Respir Crit Care Med 2012; 185:645-652.
52. Bilton D, Bellon G, Charlton B, et al. Pooled analysis of two large randomised phase III inhaled mannitol studies in cystic fibrosis. J Cyst Fibros 2013; 12: 367-376.
53. Accurso FJ, Moss RB, Wilmott RW, et al. Denufosol tetrasodium in patients with cystic fibrosis and normal to mildly impaired lung function. Am J Respir Crit Care Med 2011; 183:627-634.
54. Ratjen F, Durham T, Navratil T, et al. Long term effects of denufosol tetrasodium in patients with cystic fibrosis. J Cyst Fibros 2012; 11:539-549.
55. Qadri YJ, Rooj AK, Fuller CM. ENaCs and ASICs as therapeutic targets. Am J Physiol Cell Physiol 2012; 302:C943-C965.
56. Gianotti A, Melani R, Caci E, et al. ENaC silencing as a strategy to correc. The airway surface fluid deficit in cystic fibrosis. Am J Respir Cell Mol Biol 2013; 49:445-452.
57. Mott LS, Park J, Gangell CL, et al. Distribution of early structural lung changes due to cystic fibrosis detected with chest computed tomography. J Pediatr 2013.
58. Sly PD, Brennan S, Gangell C, et al. Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening. Am J Respir Crit Care Med 2009; 180:146-152.
59. Pillarisetti N, Williamson E, Linnane B, et al. Infection, inflammation, and lung function decline in infants with cystic fibrosis. Am J Respir Crit Care Med 2011; 184:75-81.
60. Sly PD, Gangell CL, Chen L, et al. Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med 2013; 368:1963-1970.
61. Ramsey BW, Banks-Schlegel S, Accurso FJ, et al. Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report. Am J Respir Crit Care Med 2012; 185:887-892.
62. Wielputz MO, Eichinger M, Puderbach M. Magnetic resonance imaging of cystic fibrosis lung disease. J Thorac Imaging 2013; 28:151-159.
63. Belessis Y, Dixon B, Hawkins G, et al. Early cystic fibrosis lung disease detected by bronchoalveolar lavage and lung clearance index. Am J Respir Crit Care Med 2012; 185:862-873.
64. Stocks J, Thia LP, Sonnappa S. Evaluation and use of childhood lung function tests in cystic fibrosis. Curr Opin Pulm Med 2012; 18:602-608.
65. Jensen R, Stanojevic S, Gibney K, et al. Multiple breath nitrogen washout\: A feasible alternative to mass spectrometry. PLoS One 2013; 8:e56868.
66. Hunter RC, Klepac-Ceraj V, Lorenzi MM, et al. Phenazine content in the cystic fibrosis respiratory tract negatively correlates with lung function and microbial complexity. Am J Respir Cell Mol Biol 2012; 47:738-745.
67. Patel K, Davis SD, Johnson R, Esther CR Jr. Exhaled breath condensate purines correlate with lung function in infants and preschoolers. Pediatr Pulmonol 2013; 48:182-187.
68. Griffin PE, Roddam LF, Belessis YC, et al. Expression of PPARgamma and paraoxonase 2 correlated with Pseudomonas aeruginosa infection in cystic fibrosis. PLoS One 2012; 7:e42241.
69. Sagel SD, Wagner BD, Anthony MM, et al. Sputum biomarkers of inflammation and lung function decline in children with cystic fibrosis. Am J Respir Crit Care Med 2012; 186:857-865.
70. Rowe SM, Accurso F, Clancy JP. Detection of cystic fibrosis transmembrane conductance regulator activity in early-phase clinical trials. Proc Am Thorac Soc 2007; 4:387-398.
71. Sousa M, Servidoni MF, Vinagre AM, et al. Measurements of CFTR-mediated Cl-secretion in human rectal biopsies constitute a robust biomarker for cystic fibrosis diagnosis and prognosis. PLoS One 2012; 7:e47708.