New drugs for cystic fibrosis

Expert Opinion on Investigational Drugs

Volumn 20, Issue 9, 2011, Pages 1285-1292

  Wilschanski, Michael ^a   Kerem, Eitan ^a  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

Author keywords

Corrector; Cystic fibrosis; Mutation classification; Potentiator

Indexed keywords

ATALUREN; GENTAMICIN; IVACAFTOR; TRANSMEMBRANE CONDUCTANCE REGULATOR;

CLINICAL TRIAL (TOPIC); CYSTIC FIBROSIS; DRUG BIOAVAILABILITY; DUCHENNE MUSCULAR DYSTROPHY; GENE MUTATION; GENE SEQUENCE; GENE THERAPY; GENETIC SCREENING; HIGH THROUGHPUT SCREENING; HUMAN; NONHUMAN; PATHOLOGY; REVIEW; STOP CODON;

ANIMALS; CLINICAL TRIALS AS TOPIC; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DISEASE MODELS, ANIMAL; GENE THERAPY; HUMANS; MICE;

EID: 80051727476     PISSN: 13543784     EISSN: 17447658     Source Type: Journal    
DOI: 10.1517/13543784.2011.600304     Document Type: Review

References (37)

1. Cystic Fibrosis Foundation. Patient Registry 2007 annual report. Bethesda, Maryland: cystic fibrosis foundation. Available from: http://www.cff.org/ID=4573/TYPE=2676/2004%20Patient%20Registry%20Report.pdf
2. Kerem B, Rommens JM, Buchanan WJA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science 1989;245:1073-80 (Pubitemid 19231815)
3. Rommens JM, Iannuzzi MC, Kerem B, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 1989;245:1059-65 (Pubitemid 19231813)
4. Riordan JR, Rommens JM, Kerem B, et al. Identification of the cystic fibrosis gene: cloning and characterization of the complementary DNA. Science 1989;245:1066-73 (Pubitemid 19231814)
5. Bear CE, Li CH, Kartner N, et al. Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR). Cell 1992;68:809-19
6. Available from:. http://www.genet.sickkids.on.ca/cftr/mutations.html
7. Kazazian HH Jr. Population variation of common cystic fibrosis mutations: the cystic fibrosis genetic analysis consortium. Hum Mutat. 1994;4:167-77
8. Bobadilla JL, Macek M Jr, Fine JP, Farell PM. Cystic fibrosis: a worldwide analysis of CFTR mutations-correlation with incidence data and application to screening. Hum Mutat 2002;19:575-606 (Pubitemid 34556480)
9. Zielenski J. Genotype and phenotype in cystic fibrosis. Respiration 2000;67(2):117-33 (Pubitemid 30193081)
10. Wilschanski M, Zielenski J, Markiewicz D, et al. Correlation of sweat chloride analysis with classes of CFTR gene mutations. J Pediatr 1995;127:705-10
11. Bartlett JR, Friedman KJ, Ling SC, et al. Genetic modifiers of liver disease in cystic fibrosis. JAMA 2009;302:1076-83
12. Drumm ML, Constan MW, Schluchter MD, et al. Genetic modifiers of lung disease in cystic fibrosis. N Engl J Med 2005;353(14):1443-53 (Pubitemid 41400918)
13. Davies JC, Alton EWFW. Gene therapy for cystic fibrosis. Proc Am Thorac Soc 2010;7:408-14 •• An excellent update and review of the subject.
14. Farinha CM, Nogueira P, Mendes F, et al. The human DNAJ homologue (Hdj-1/heat-shock protein (Hsp) 40 cochaperone is required for the in vivo stabilization of the cystic fibrosis transmembrane conductance regulator by Hsp70. Biochem J 2002;366:797-806
15. Pedemonte N, Lukacs GL, Du K, et al. Small-molecule correctors of defective DF508-CFTR cellular processing identified by high-throughput screening. J Clin Invest 2005;115:2564-71 (Pubitemid 41266219)
16. Varga K, Goldstein RF, Jurkuvenaite A, et al. Enhanced cell-surface stability of rescued DF508 cystic fibrosis transmembrane conductance regulator (CFTR) by pharmacological chaperones. Biochem J 2008;410:555-64 (Pubitemid 351429026)
17. Clancy JP, Spencer-Green G; for the VX-809-101 Study Group. Clinical Evaluation of VX-809, a novel investigational oral F508del-CFTR corrector, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. JCF 2010;9(Suppl 1A):73
18. Van Goor F, Hadida S, Grootenhuis PDJ, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. PNAS 2009;106:18825-30 •• Basic studies which were the foundation of VX-770 clinical studies.
19. 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
20. Kerem B, Chiba-Falek O, Kerem E. Cystic fibrosis in Jews: frequency and mutation distribution. Genet Test 1997;1:35-9 (Pubitemid 127526935)
21. Hermann T. Aminoglycoside antibiotics: old drugs and new therapeutic approaches. Cell Mol Life Sci 2007;64:1841-52 (Pubitemid 47096588)
22. Gorini L, Kataja E. Phenotypic repair by streptomycin of defective genmotypes in E Coli. Proc Natl Acad Sci USA 1964;51:487-93
23. Howard M, Frizzel RA, Bedwell DM. Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations. Nat Med 1996;2:467-9 (Pubitemid 26191920)
24. Bedwell DM, Kaenjak A, Benos DJ, et al. Suppression of a CFTR premature stop mutation in a bronchial epithelial cell line. Nat Med 1997;3:1280-4 (Pubitemid 27508832)
25. Barton-Davis ER, Cordier L, Shoturma DI, et al. Aminoglycoside antibiotics restore dystrophin function to skeletal muscle of mdx mice. J Clin Invest 1999;104:3745-81
26. Du M, Jones JR, Lanier J, et al. Aminoglycoside suppression of a premature stop mutation in a Cftr-/-mouse carrying CFTR-G542X transgene. J Mol Med 2002;80:595-604
27. Wilschanski M, Famini C, Blau H, et al. A pilot study of the effect of gentamicin on nasal potential difference measurements in cystic fibrosis patients carrying stop mutations. Am J Respir Crit Care Med 2001;163:1683-92
28. Wilschanski M, Yahav Y, Yaakov Y, et al. Gentamicin-induced correction of of CFTR function in patients with cystic fibrosis and CFTR stop mutations. N Engl J Med 2003;349:1433-41 (Pubitemid 37211058)
29. Clancy JP, Bebok Z, Ruiz F, et al. Evidence that systemic gentamicin suppresses premature stop mutations in patients with cystic fibrosis. Am J Respir Crit Care Med 2001;163:1683-92 (Pubitemid 32578776)
30. Sermet-Gaudilus 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
31. Linde L, Boelz S, Nissim-Rafinia M, et al. Ninsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin. J Clin Invest 2007;117:1-9
32. Welch E, Barton ER, Zhuo J, et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature 2007;447:87-91 (Pubitemid 46685839)
33. Du M Liu X, Welch EM, et al. PTC124is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model. Proc Natl Acad Sci USA 2008;105:2064-9 (Pubitemid 351439465)
34. 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;372:719-27
35. Wilschanski M, Miller LL, Shoseyov D, et al. Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis. ERJ Express 2011; published on January 13, 2011 as; doi: 10.1183/09031936.00120910
36. Sermet-Gaudelus I, De Boeck K, Casimir G, et al. Ataluren (PTC124) induces CFTR protein expression and activity in children with nonsense-mutation cystic fibrosis. Am J Respir Care Med 2010;182(10):1262-72 •• A pediatric study of PTC 124 in CF with good review of previous studies.
37. Finkel R, Wong B, Bushby K, et al. Results of Phase 2b dose-ranging study of Ataluren (PTC124) in nonsense mutation Duchenne/Becker muscular dystrophy. Poster 3.51 International Congress of World Muscle Society, Kumamoto, Japan, October 2010