Emerging drug treatments for cystic fibrosis

Expert Opinion on Emerging Drugs

Volumn 8, Issue 2, 2003, Pages 523-535

  Zeitlin, Pamela L ^a  

^a JOHNS HOPKINS HOSPITAL   (United States)

Author keywords

Antibiotics; Antimicrobial peptide; Butyrates; Chaperones; Chloride; Gene therapy; Genetic; Genomics; High throughput screening; Inflammation; Isoflavones; Mucolytic; Mutation; Proteomics; Vaccine

Indexed keywords

4 PHENYLBUTYRIC ACID; 8 CYCLOPENTYL 1,2 DIPROPYLXANTHINE; ADEK; ADENOSINE A1 RECEPTOR ANTAGONIST; AMINOGLYCOSIDE ANTIBIOTIC AGENT; ANTIBIOTIC AGENT; ANTIFUNGAL AGENT; AZTREONAM; CEFTAZIDIME; CEPHALOSPORIN DERIVATIVE; CHLORIDE CHANNEL; CHLORIDE CHANNEL BLOCKING AGENT; DORNASE ALFA; GAMMA1B INTERFERON; GENISTEIN; GLYCEROL; IB 367; ISOBUTYLMETHYLXANTHINE; ISOFLAVONE DERIVATIVE; KREON; MACROLIDE; PANCRECARB; PANCRELIPASE; PENICILLIN DERIVATIVE; PROTEIN TYROSINE KINASE INHIBITOR; QUINOLONE DERIVATIVE; RECOMBINANT GAMMA INTERFERON; TALNIFLUMATE; THAPSIGARGIN; TICARCILLIN; TOBRAMYCIN; TRANSMEMBRANE CONDUCTANCE REGULATOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VITAMAX; VITAMIN;

ACUTE KIDNEY FAILURE; BIOGENESIS; CLINICAL TRIAL; CYSTIC FIBROSIS; DEVICE; DRUG TARGETING; GENE DISRUPTION; GENE MUTATION; HUMAN; INFECTION; INFLAMMATION; LUNG DISEASE; MORBIDITY; MORTALITY; NEPHROTOXICITY; NONHUMAN; OTOTOXICITY; PHARMACOGENOMICS; PHYSIOTHERAPY; PROTEOMICS; REVIEW; SCREENING;

ANTI-INFECTIVE AGENTS; ANTI-INFLAMMATORY AGENTS; CHLORIDE CHANNELS; CHLORIDES; CLINICAL TRIALS; CODON, TERMINATOR; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DRUG DESIGN; GENE THERAPY; HUMANS; MUTATION; PROTEIN FOLDING;

EID: 0347627794     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.8.2.523     Document Type: Review

References (150)

1. RIORDAN JR, ROMMENS JM, KEREM B et al.: Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA [published erratum appears in Science (1989) 245(4925):1437]. Science (1989) 245:1066-1073.
2. RIORDAN JR, ROMMENS JM, KEREM B et al.: Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA [published erratum appears in Science (1989) 245(4925):1437]. Science (1989) 245:1066-1073.
3. QUINTON PM: Physiological basis of cystic fibrosis: a historical perspective. Physiol. Rev. (1999) 79(1 Suppl.):S3-S22.
4. AITKEN ML, BURKE W, MCDONALD G, SHAK S, MONTGOMERY AB, SMITH A: Recombinant human DNase inhalation in normal subjects and patients with cystic fibrosis. A Phase I study. JAMA (1992) 267:1947-1951.
5. CONWAY SP, WATSON A: Nebulised bronchodilators, corticosteroids, and rhDNase in adult patients with cystic fibrosis. Thorax (1997) 52(Suppl. 2):S64-S68.
6. SHAK S, CAPON DJ, HELLMISS R, MARSTERS SA, BAKER CL: Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum. Proc. Natl. Acad. Sci. USA (1990) 87:9188-9192.
7. CHURCH DA, KANGA JF, KUHN RJ et al.: Sequential ciprofloxacin therapy in pediatric cystic fibrosis: comparative study versus cefrazidime/tobramycin in the treaunent of acute pulmonary exacerbations. The Cystic Fibrosis Study Group. Pediatr. Infect. Dis. J. (1997) 16(1):97-105; discussion 123.
8. MCLAUGHLIN FJ, MATTHEWS WJ JR, STRIEDER DJ et al.: Clinical and bacteriological responses to three antibiotic regimens for acute exacerbations of cystic fibrosis: ticarcillin-tobramycin, azlocillin-tobramycin, and azlocillin-placebo. J. Infect. Dis. (1983) 147:559-567.
9. KILBY JM, GILLIGAN PH, YANKASKAS JR, HIGHSMITH WE JR, EDWARDS LJ, KNOWLES MR: Nontuberculous mycobacteria in adult patients with cystic fibrosis. Chest (1992) 102:70-75.
10. MILLER PW, HAMOSH A, MACEK M JR et al.: Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in allergic bronchopulmonary aspergillosis. Am. J. Hum. Genet. (1996) 59(1):45-51.
11. FITZPATRICK SB, ROSENSTEIN BJ: Moxalactam-tobramycin-resistant Pseudomonas aeruginosa isolates in patients with cystic fibrosis. Clin. Pediatr. (Phil.) (1983) 22:628-630.
12. RAMSEY BW, DORKIN HL, EISENBERG JD et al.: Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N. Engl. J. Med. (1993) 328:1740-1746.
13. SMITH AL, RAMSEY BW, HEDGES DL et al.: Safety of aerosol tobramycin administration for 3 months to patients with cystic fibrosis. Pediatr. Pulmonol. (1989) 7:265-271.
14. TOUW DJ, JACOBS FA, BRIMICOMBE RW, HEIJERMAN HG, BAKKER W, BRIEMER DD: Pharmacokinetics of aerosolized tobramycin in adult patients with cystic fibrosis. Antimicrob. Agents Chemother. (1997) 41(I):184-187.
15. WANG X, MOYLAN B, LEOPOLD DA et al.: Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population. JAMA (2000) 284(14):1814-1819. A case control study conducted in a large otolaryngology, head and neck surgery clinic in the US revealed that mutations or polymorphisms in CFTR may be associated with development of chronic rhinosinusitis in the general population.
16. ANGUIANO A, OATES RD, AMOS JA et al.: Congenital bilateral absence of the vas deferens. A primarily genital form of cystic fibrosis. JAMA (1992) 267:1794-1797.
17. COLIN AA, SAWYER SM, MICKLE JE, OATES RD, MILUNSKY A, AMOS JA: Pulmonary function and clinical observations in men with congenital bilateral absence of the vas deferens. Chest (1996) 110(2):440-445.
18. DORK T, DWORNICZAK B, AULEHLA-SCHOLZ C et al.: Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens. Hum. Genet. (1997) 100(3-4):365-377.
19. GOSHEN R, KEREM E, SHOSHANI T et al.: Cystic fibrosis manifested as undescended testis and absence of vas deferens. Pediatrics (1992) 90:982-983.
20. WELSH MJ, SMITH AE: Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell (1993) 73:1251-1254.
21. NO AUTHORS LISTED: Correlation between genotype and phenotype in patients with cystic fibrosis. The Cystic Fibrosis Genotype-Phenotype Consortium [see comments]. N. Engl. J. Med. (1993) 329(18):1308-1313.
22. CHENG SH, GREGORY RJ, MARSHALL J et al.: Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell (1990) 63:827-834.
23. CHENG SH, FANG SL, ZABNER J et al.: Functional activation of the cystic fibrosis trafficking mutant delta F508-CFTR by overexpression. Am. J. Physiol. (1995) 268:L615-L624.
24. JENSEN TJ, LOO MA, PIND S, WILLIAMS DB, GOLDBERG AL, RIORDAN JR: Multiple proteolytic systems, induding the proteasome, contribute to CFTR processing. Cell (1995) 83:129-135.
25. LOO MA, JENSEN TJ, CUI L, HOU Y, CHANG XB, RIORDAN JR: Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome. EMBO J. (1998) 17(23):6879-6887.
26. WARD CL, OMURA S, KOPITO RR: Degradation of CFTR by the ubiquitin-proteasome pathway. Cell (1995) 83:121-127.
27. OSTEDGAARD LS, ZEIHER B, WELSH MJ: Processing of CFTR bearing the P574H mutation differs from wild-type and deltaF508-CFTR. J. Cell Sci. (1999) 112(Pt 13):2091-2098.
28. CHOO-KANG LR, ZEITLIN PL: Type I, II, III, IV and V cystic fibrosis transmembrane conductance regulator defects and opportunities for therapy. Curr. Opin. Pulm. Med. (2000) 6(6):521-529.
29. LI C, RAMJEESINGH M, REYES E et al.: The cystic fibrosis mutation (delta F508) does not influence the chloride channel activity of CFTR. Nat. Genet. (1993) 3:311-316.
30. PASYK EA, FOSKETT JK: Mutant (delta F508) cystic fibrosis transmembrane conductance regulator Cl- channel is functional when retained in endoplasmic reticulum of mammalian cells. J. Biol. Chem. (1995) 270(21):12347-12350.
31. MICKLE JE, CUTTING GR: Clinical implications of cystic fibrosis transmembrane conductance regulator mutations. Clin. Chest Med. (1998) 19(3):443-458.
32. HAARDT M, BENHAROUGA M, LECHARDEUR D, KARTNER N, LUKACS GL: C-terminal truncations destabilize the cystic fibrosis transmembrane conductance regulator without impairing its biogenesis. A novel class of mutation. J. Biol. Chem. (1999) 274(31):21873-21877.
33. HARTL FU, HAYER-HARTL M: Molecular chaperones in the cytosol: from nascent chain to folded protein. Science (2002) 295(5561):1852-1858.
34. BROWN CR, HONG-BROWN LQ, WELCH WJ: Correcting temperature-sensitive protein folding defects. J. Clin. Invest. (1997) 99(6):1432-1444.
35. DENNING GM, ANDERSON MP, AMARA JF, MARSHALL J, SMITH AE, WELSH MJ: Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive [see comments]. Nature (1992) 358:761-764.
36. EGAN ME, SCHWEIBERT EM, GUGGINO WB: Differential expression of ORCC and CFTR induced by low temperature in CF airway epithelial cells. Am. J. Physiol. (Cell. Physiol.) (1995) 268(37):C243-C251.
37. SHARMA M, BENHAROUGA M, HU W, LUKACS GL: Conformational and temperature-sensitive stability defects of the delta F508 cystic fibrosis transmembrane conductance regulator in post-endoplasmic reticulum compartments. J. Biol. Chem. (2001) 276(12):8942-8950.
38. BROWN CR, HONG-BROWN LQ, BIWERSI J, VERKMAN AS, WELCH WJ: Chemical chaperones correct the mutant phenotype of the delta F508 cystic fibrosis transmembrane conductance regulator protein. Cell Stress Chaperones (1996) 1(2):117-125.
39. GEKKO K, TIMASHEFF SN: Mechanism of protein stabilization by glycerol: preferential hydration in glycerol-water mixtures. Biochemistry (Mosc.) (1981) 20(16):4667-4676.
40. HARA M, VERKMAN AS: Glycerol replacement corrects defective skin hydration, elasticity, and barrier function in aquaporin-3-deficient mice. Proc. Natl. Acad. Sci. USA (2003) 100(12):7360-7365.
41. ASHKENAS J, BYERS PH: The final stage of gene expression: chaperones and the regulation of protein fate. Am. J. Hum. Genet. (1997) 61(2):267-272.
42. HARTL FU: Molecular chaperones in cellular protein folding. Nature (1996) 381(6583):571-579.
43. BERCOVICH B, STANCOVSKI I, MAYER A et al.: Ubiquitin-dependent degradation of certain protein substrates in vitro requires the molecular chaperone Hsc70. J. Biol. Chem. (1997) 272(14):9002-9010.
44. SATO S, WARD CL, KOPITO RR: Cotranslational ubiquitination of cystic fibrosis transmembrane conductance regulator in vitro. J. Biol. Chem. (1998) 273(13):7189-7192.
45. CLEJAN LA, CEDERBAUM AI: Role of iron, hydrogen peroxide and reactive oxygen species in microsomal oxidation of glycerol to formaldehyde. Arch. Biochem. Biophys. (1991) 285(1):83-89.
46. WANG JC, KANIM LE, NAGAKAWA IS, YAMANE BH, VINTERS HV, DAWSON EG: Dose-dependent toxicity of a commercially available demineralized bone matrix material. Spine (2001) 26(13):1429-1435.
47. RUBENSTEIN RC, ZEITLIN PL: A pilot dinical trial of sodium 4-phenylbutyrate (Buphenyl) in delta F508-homozygous cystic fibrosis patients: evidence of restoration of nasal epithelial CFTR function. Am. J. Resp. Crit. Care Med. (1998) 157:484490.
48. ZEITLIN PL, DIENER-WEST M, RUBENSTEIN RC, BOYLE MP, LEE CK, BRASS-ERNST L: Evidence of CFTR function in cystic fibrosis after systemic administration of 4-phenylbutyrate. Mol. Ther. (2002) 6(1):119-126. A randomised, double-blind, placebo-controlled, dose-escalation and safety study in adults with CF demonstrated that oral 4-phenylbutyrate administration was associated with restoration of chloride transport in nasal epithelia.
49. BRUSILOW S, TINKER J, BATSHAW ML: Amino acid acylation: a mechanism of nitrogen excretion in inborn errors of urea synthesis. Science (1980) 207(4431):659-661.
50. BRUSILOW SW: Phenylacetylglutamine may replace urea as a vehicle for waste nitrogen excretion. Pediatr. Res. (1991) 29:147-150.
51. CANDIDO EP, REEVES R, DAVIE JR: Sodium butyrate inhibits histone deacetylation in cultured cells. Cell (1978) 14(1):105-113.
52. CONSTANTOULAKIS P, KNITTER G, STAMATOYANNO POULOS G: Butyrate stimulates HbF in adult baboons. Prog. Clin. Biol. Res. (1989) 316B:351-361.
53. CONSTANTOULAKIS P, KNITTER G, STAMATOYANNOPOULOS G: On the induction of fetal hemoglobin by butyrates: in vivo and in vitro studies with sodium butyrate and comparison of combination treatments with 5-AzaC and AraC. Blood (1989) 74:1963-1971.
54. EBERT MN, BEYER-SEHLMEYER G, LIEGIBEL UM, KAUTENBURGER T, BECKER TW, POOL-ZOBEL BL: Butyrate induces glutathione S-transferase in human colon cells and protects from genetic damage by 4-hydroxy-2-nonenal. Nutr. Cancer (2001) 41(1-2):156-164.
55. HUDGINS WR, FIBACH E, SAFAYA S, RIEDER RF, MILLER AC, SAMID D: Transcriptional upregulation of gamma-globin by phenylbutyrate and analogous aromatic fatty acids. Biochem. Pharmacol. (1996) 52(8):1227-1233.
56. NEWMARK HL, YOUNG CW: Butyrate and phenylacetate as differentiating agents: practical problems and opportunities. J. Cell. Biochem. Suppl. (1995) 22:247-253.
57. PERRINE SP, OLIVIERI NF, FALLER DV, VICHINSKY EP, DOVER GJ, GINDER GD: Butyrate derivatives. New agents for stimulating fetal globin production in the beta-globin disorders. Am. J. Pediatr. Hematol. Oncol. (1994) 16:67-71.
58. SHER GD, GINDER GD, LITTLE J, YANG S, DOVER GJ, OLIVIERI NF: Extended therapy with intravenous arginine butyrate in patients with beta-hemoglobinopathies [see comments]. N. Engl. J. Med. (1995) 332(24):1606-1610.
59. CHOO-KANG LR, ZEITLIN PL: Induction of HSP70 promotes DeltaF508 CFTR trafficking. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) 281(1):L58-L68.
60. RUBENSTEIN RC, EGAN ME, ZEITLIN PL: In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR. J. Clin. Invest. (1997) 100:2457-2465.
61. RUBENSTEIN RC, ZEITLIN PL: Sodium 4-phenylbutyrate downregulates Hsc70: implications for intracellular trafficking of DeltaF508-CFTR. Am. J. Physiol. Cell. Physiol. (2000) 278(2):C259-C267.
62. RUBENSTEIN RC, ZEITLIN PL: Use of protein repair therapy in the treatment of cystic fibrosis. Curr. Opin. Pediatr. (1998) 10(3):250-255.
63. ARISPE N, MA J, JACOBSON KA, POLLARD HB: Direct activation of cystic fibrosis transmembrane conductance regulator channels by 8-cyclopentyl-1,3-dipropylxanthine (CPX) and 1,3-diallyl-8-cyclohexylzanthine (DAX). J. Biol. Chem. (1997) 273:5727-5734.
64. CASAVOLA V, TURNER RJ, GUAY-BRODER C, JACOBSON KA, EIDELMAN O, POLLARD HB: CPX, a selective A1-adenosine-receptor antagonist, regulates intracellular pH in cystic fibrosis cells. Am. J. Physiol. (1995) 269(1 Pt 1):C226-C233.
65. SRIVASTAVA M, EIDELMAN O, POLLARD HB: Pharmacogenomics of the cystic fibrosis transmembrane conductance regulator (CFTR) and the cystic fibrosis drug CPX using genome microarray analysis. Mol. Med. (1999) 5(11):753-767. Comparative genomics of wild-type and CF human epithelial cells were studied in the presence or absence of CPX and identified a gene pattern in common between wild-type and CPX-treated conditions.
66. MCCARTY NA, STANDAERT TA, TERESI M et al.: A Phase I randomized, multicenter trial of CPX in adult subjects with mild cystic fibrosis. Pediatr. Pulmonol. (2002) 33(2):90-98.
67. FRENCH PJ, BIJMAN J, BOT AG, BOOMAARS WEM, SCHOLTE BJ, DEJONGE HR: Genistein activates CFTR-Cl- channels via a tyrosine kinase-and protein phosphatase-independent mechanism. Am. J. Physiol. (Cell Physiol) (1997) 273(2 Pt 1):C747-C753.
68. HWANG TC, WANG F, YANG IC, REENSTRA WW: Genistein potentiates wild-type and delta F508-CFTR channel activity. Am. J. Physiol. (1997) 273(3 Pt 1):C988-C998.
69. ILLEK B, FISCHER H, SANTOS GF, WIDDICOMBE JH, MACHEN TE, REENSTRA WW: cAMP-independent activation of CFTR Cl channels by the tyrosine kinase inhibitor genistein. Am. J. Physiol. (1995) 268(4 Pt 1):C886-C893.
70. ILLEK B, ZHANG L, LEWIS NC, MOSS RB, DONG JY, FISCHER H: Defective function of the cystic fibrosis-causing missense mutation G551D is recovered by genistein. Am. J. Physiol. (1999) 277(4 Pt 1):C833-C839.
71. WEINREICH F, WOOD PG, RIORDAN JR, NAGEL G: Direct action of genistein on CFTR. Pflugers Arch. (1997) 434(4):484-491.
72. TABARY O, ESCOTTE S, COUETIL JP et al.: Genistein inbibits constitutive and inducible NFkappaB activation and decreases IL-8 production by human cystic fibrosis bronchial gland cells. Am. J. Pathol. (1999) 155(2):473-481.
73. SUAUD L, LI J, JIANG Q, RUBENSTEIN RC, KLEYMAN TR: Genistein restores functional interactions between Delta F508-CFTR and ENaC in Xenopus oocytes. J. Biol. Chem. (2002) 277(11):8928-8933.
74. ANDERSSON C, ROOMANS GM: Activation of deltaF508 CFTR in a cystic fibrosis respiratory epithelial cell line by 4-phenylbutyrate, genistein and CPX. Eur. Respir. J. (2000) 15(5):937-941.
75. EGAN ME, GLOCKNER-PAGEL J, AMBROSE CA et al.: Calcium-pump inhibitors induce functional surface expression of delta F508-CFTR protein in cystic fibrosis epithetial cells. Nat. Med. (2002) 8(5):485-492. Thapsigargin in vitro and in vivo in a murine mouse model restored ΔF508 CFTR to the cell surface.
76. CHU S, ZEITLIN PL: Alternative mRNA splice variants of the rat ClC-2 chloride channel gene are expressed in lung: genomic sequence and organization of ClC-2. Nucleic Acids Res. (1997) 25(20):4153-4159.
77. CUPPOLETTI J, TEWARI KP, SHERRY AM, KUPERT EY, MALINOWSKA DH: ClC-2 Cl- channels in human lung epithelia: activation by arachidonic acid, amidation, and acid-activated omeprazole. Am. J. Physiol. Cell. Physiol. (2001) 281(1):C46-C54. Activation of ClC-2 chloride channels with acid-activated omeprazole in cell cultures from healthy volunteers and CF patients suggests a potential new therapeutic target.
78. SCHWIEBERT EM, CID LP, CARTER M, STAFFORD D, GUGGINO WB, CUTTING GR: Human ClC-2 forms a voltage-sensitive and pH-regulated chloride channel when expressed in human CF airway epithelial cells. Pediatr. Pulmonol. (1996) S13:236-236.
79. SCHWIEBERT EM, CID-SOTO LP, STAFFORD D et al.: Analysis of ClC-2 channels as an alternative pathway for chloride conduction in cystic fibrosis airway cells. Proc. Natl. Acad. Sci. USA (1998) 95(7):3879-3884.
80. ANDERSON MP, WELSH MJ: Calcium and cAMP activate different chloride channels in the apical membrane of normal and cystic fibrosis epithelia. Proc. Natl. Acad. Sci. USA (1991) 88:6003-6007.
81. BOUCHER RC, CHENG EH, PARADISO AM, STUTTS MJ, KNOWLES MR, EARP HS: Chloride secretory response of cystic fibrosis human airway epithelia. Preservation of calcium but not protein kinase C- and A-dependent mechanisms. J. Clin. Invest. (1989) 84:1424-1431.
82. KNOWLES MR, CLARKE LL, BOUCHER RC: Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis [see comments]. N. Engl. J. Med. (1991) 325:533-538.
83. KNOWLES MR, CLARKE LL, BOUCHER RC: Extracellular ATP and UTP induce chloride secretion in nasal epithelia of cystic fibrosis patients and normal subjects in vivo. Chest (1992) 101:60S-63S.
84. CLOUTIER MM, GUERNSEY L, MATTES P, KOEPPEN B: Duramycin enhances chloride secretion in airway epithelium. Am. J. Physiol. (1990) 259:C450-C454.
85. CLOUTIER MM, GUERNSEY L, SHA'AFI RI: Duramycin increases intracellular calcium in airway epithelium. Membr. Biochem. (1993) 10:107-118.
86. HENKE DC, STUTTS MJ, HARVEY R, MOLINA L: Bioelectric and fluid transport effects of the nonadecapeptide 2622U90 (Duramycin) in normal human cystic fibrosis airway epithelium and anine airways. Pediatr. Pulmonol. Suppl. (1998) 17:238.
87. MCNULTY MJ, HUTABARAT RH, HARVEY R, MOLINA Y VEDIA L: The pharmacokinetics and tissue distribution of the nonadecapeptide, duramycin, in the rat and mouse. Proceedings 8th North American Meeting of the International Society for the Study of Xenobiotics (1997) 12:122-122.
88. ZEITLIN PL, GUGGINO WB, MOLINA L: Activation by the nonadecapeptide 2622U90 (duramycin) of chloride secretion in healthy volunteers and patients with cystic fibrosis. Pediatr. Pulmonol. (1998) 17:277-277.
89. TIETZ PS, MARINELLI RA, CHEN XM et al.: Agonist-induced coordinated trafficking of functionally related transport proteins for water and ions in cholangiocytes. J. Biol. Chem. (2003) 278(22):20413-20419.
90. GRUBER AD, ELBLE RC, JI HL, SCHREUR KD, FULLER CM, PAULI BU: Genomic cloning, molecular characterization, and functional analysis of human CLCA1, the first human member of the family of Ca2+-activated Cl- channel proteins. Genomics (1998) 54(2):200-214.
91. HAUBER HP, MANOUKIAN JJ, NGUYEN LH et al.: Increased expression of interleukin-9, interleukin-9 receptor, and the calcium-activated chloride channel hCLCA1 in the upper airways of patients with cystic fibrosis. Laryngoscope (2003) 113(6):1037-1042.
92. ZHOU Y, SHAPIRO M, DONG Q et al.: A calcium-activated chloride channel blocker inhibits goblet cell metaplasia and mucus overproduction. Novartis Found. Symp. (2002) 248:150-165.
93. KEELING KM, BEDWELL DM: Clinically relevant aminoglycosides can suppress disease-associated premature stop mutations in the IDUA and P53 cDNAs in a mammalian translation system. J. Mol. Med. Immun. (2002) 80(6):367-376.
94. MANUVAKHOVA M, KEELING K, BEDWELL DM: Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translation system. RNA - A Publication of the RNA Society (2000) 6(7):1044-1055.
95. HOWARD M, FRIZZELL DM, BEDWELL DM: Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations. Nat. Med. (1996) 2(4):467-469. Two common CFTR stop codon mutations can be suppressed by treating cells with low-dose gentamicin.
96. CLANCY JP, BEBOK Z, JONES J et al.: Evidence that systemic gentamicin suppresses premature stop codon mutations in patients with cystic fibrosis. Am. J. Respir. Crit. Care Med (2003) 163(7):1683-1692. Intravenous gentamicin treatment produced small increases in nasal epithelial chloride transport in CF patients with stop codon mutations.
97. 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. (2000) 161(3 Pt 1):860-865. Topical gentamicin drops are associated with modest increases in nasal epithelial chloride transport in CF patients with stop codon mutations.
98. SCHROEDER TH, LEE MM, YACONO PW et al.: CFTR is a pattern recognition molecule that extracts Pseudomonas aeruginosa LPS from the outer membrane into epithelial cells and activates NF-kappa B translocation. Proc. Natl. Acad Sci. USA (2002) 99(10):6907-6912.
99. COLEMAN FT, MUESCHENBORN S, MELULENI G et al: Hypersusceptibility of cystic fibrosis mice to chronic Pseudomonas aeruginosa oropharyngeal colonization and lung infection. Proc. Natl. Acad. Sci. USA. (2003) 100(4):1949-1954.
100. RYAN G, MUKHOPADHYAY S, SINGH M: Nebulised anti-pseudomonal antibiotics for cystic fibrosis. Cochrane Database Syst. Rev. (2000) 2:CD001021.
101. GIBSON RL, EMERSON J, MCNAMARA S et al.: Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis. Am. J. Respir. Crit. Care Med. (2003) 167(6):841-849. A double-blind, placebo-controlled, multi-centre, randomised trial to test the efficacy of inhaled tobramycin over a 28-day period to infants and children with CF led to a reduction in P. aeruginosa in bronchoalveolar lavage fluid.
102. CHIU CH, WONG S, HANCOCK RE, SPEERT DP: Adherence of Burkholderia cepacia to respiratory tract epithelial cells and inhibition with dextrans. Microbiology (2001) 147(10):2651-2658. Dextrans inhibit adherence of B. cepacia to respiratory epithelial cells.
103. ROTHSTEIN DM, SPACCIAPOLI P, TRAN LT et al.: Anticandida activity is retained in P-113, a 12-amino-acid fragment of histatin 5. Antimicrob. Agents Chemother. (2001) 45(5):1367-1373.
104. GILES FJ, MILLER CB, HURD DD et al.: A Phase III, randomized, double-blind, placebo-controlled, multinational trial of iseganan for the prevention of oral mucositis in patients receiving stomatotoxic chemotherapy (PROMPT-CT trial). Leuk. Lymphoma (2003) 44(7):1165-1172.
105. KONSTAN MW, DAVIS PB: Pharmacological approaches for the discovery and development of new anti-inflammatory agents for the treatment of cystic fibrosis. Adv. Drug Deliv. Rev. (2002) 54(11):1409-1423.
106. EIGEN H, ROSENSTEIN BJ, FITZSIMMONS S, SCHIDLOW DV: A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. Cystic Fibrosis Foundation Prednisone Trial Group. J. Pediatr. (1995) 126(4):515-523.
107. ROSENSTEIN BJ, EIGEN H: Risks of alternate-day prednisone in patients with cystic fibrosis. Pediatrics (1991) 87:245-246.
108. LAI HC, FITZSIMMONS SC, ALLEN DB et al.: Risk of persistent growth impairment after alternate-day prednisone treatment in children with cystic fibrosis. N. Engl. J. Med. (2000) 342(12):851-859.
109. KONSTAN MW, BYARD PJ, HOPPEL CL, DAVIS PB: Effect of high-dose ibuprofen in patients with cystic fibrosis. N. Engl. J. Med. (1995) 332(13):848-854.
110. LAWRENCE RH, SORRELL TC: Eicosapentaenoic acid modulates neutrophil leukotriene B4 receptor expression in cystic fibrosis. Clin. Exp. Immunol. (1994) 98(1):12-16.
111. BIRKE FW, MEADE CJ, ANDERSKEWITZ R, SPECK GA, JENNEWEIN HM: In vitro and in vivo pharmacological characterization of BIIL 284, a novel and potent leukotriene B(4) receptor antagonist. J. Pharmacol. Exp. Ther. (2001) 297(1):458-466.
112. PORTAL BC, RICHARD MJ, FAURE HS, HADJIAN AJ, FAVIER AE: Altered antioxidant status and increased lipid peroxidation in children with cystic fibrosis. Am. J. Clin. Nutr. (1995) 61(4):843-847.
113. RAHMAN I, MACNEE W: Oxidative stress and regulation of glutathione in lung inflammation. Eur. Respir. J. (2000) 16(3):534-554.
114. BOWLER RP, CRAPO JD: Oxidative stress in airways: is there a role for extracellular superoxide dismutase? Am. J. Respir. Crit. Care Med. (2002) 166(12 Pt 2):S38-S43.
115. WILMOTT RW, KITZMILLER JA, SZABO C, SOUTHAN GJ, SALZMAN AL: Mercaptoethylguanidine inhibits the inflammatory response in a murine model of chronic infection with Pseudomonas aeruginosa. J. Pharmacol. Exp. Ther. (2000) 292(1):88-95.
116. HOMOLYA L, VARADI A, SARKADI B: Multidrug resistance-associated proteins: export pumps for conjugates with glutathione, glucuronate or sulfate. Biofactors (2003) 17(1-4):103-114.
117. KOGAN I, RAMJEESINGH M, LI C et al.: CFTR directly mediates nudeotide-regulated glutathione flux. EMBO J. (2003) 22(9):1981-1989. Membrane vesicles containing CFTR mediate nucleotide-activated glutathione flux, suggesting a role for glutathione in CF lung disease.
118. SNYDER AH, MCPHERSON ME, HUNT JF, JOHNSON M, STAMLER JS, GASTON B: Acute effects of aerosolized S-nitrosoglutathione in cystic fibrosis. Am. J. Respir. Crit. Care Med. (2002) 165(7):922-926.
119. JOHNSON LG, BOYLES SE, WILSON J, BOUCHER RC: Normalization of raised sodium absorption and raised calcium-mediated chloride secretion by adenovirus-mediated expression of cystic fibrosis transmembrane conductance regulation in primary human cystic fibrosis airway epithelial cells. J. Clin. Invest. (1995) 95:1377-1382.
120. ROSENFELD MA, CHU CS, SETH P et al.: Gene transfer to freshly isolated human respiratory epithelial cells in vitro using a replication-deficient adenovirus containing the human cystic fibrosis transmembrane conductance regulator cDNA. Hum. Gene Ther. (1994) 5:331-342.
121. MACVINISH LJ, GILL DR, HYDE SC et al.: Chloride secretion in the trachea of null cystic fibrosis mice: the effects of transfection with pTrial10-CFTR2. J. Physiol. (Lond) (1997) 499(Pt 3):677-687.
122. HYDE SC, GILL DR, HIGGINS CF et al.: Correction of the ion transport defect in cystic fibrosis transgenic mice by gene therapy. Nature (1993) 362:250-255.
123. DRUMM ML, POPE RA, CLIFF WH et al.: Correction of the cystic fibrosis defect in vitro by retrovirus-mediated gene transfer [published erratum appears in Cell (1993) 74(1):215]. Cell (1990) 62:1227-1233.
124. DRUMM ML, POPE RA, CLIFF WH et al.: Correction of the cystic fibrosis defect in vitro by retrovirus-mediated gene transfer [published erratum appears in Cell (1993) 74(1):215]. Cell (1990) 62:1227-1233.
125. CONRAD C, AFIONE S, GUGGINO W: Administration of AAV-CFTR vectors to the airway epithelium of non-human primates is safe and efficacious. Am. J. Respir. Crit. Care Med. (1994) 149:A236-A236.
126. CONRAD CK, ALLEN SS, AFIONE SA et al.: Safety of a single-dose administration of an adeno-associated virus (AAV)-CFTR vector in the primate lung. Gene Ther. (1996) 3(8):658-668.
127. ENGELHARDT JF, SIMON RH, YANG Y et al.: Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates: biological efficacy study. Hum. Gene Ther. (1993) 4:759-769.
128. ENGELHARDT JF, YANG Y, STRATFORD-PERRICAUDET LD et al.: Direct gene transfer of human CFTR into human bronchial epithelia of xenografts with E1-deleted adenoviruses. Nat. Genet. (1993) 4:27-34.
129. FLOTTE TR, AFIONE SA, CONRAD C et al.: Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector. Proc. Natl. Acad. Sci. USA (1993) 90:10613-10617.
130. ZABNER J, PETERSEN DM, PUGA AP et al.: Safety and efficacy of repetitive adenovirus-mediated transfer of CFTR cDNA to airway epithelia of primates and cotton rats. Nat. Genet. (1994) 6:75-83.
131. YOSHIMURA K, ROSENFELD MA, NAKAMURA H et al.: Expression of the human cystic fibrosis transmembrane conductance regulator gene in the mouse lung after in vivo intratracheal plasmid-mediated gene transfer. Nucleic Acids Res. (1992) 20:3233-3240.
132. SIMON RH, ENGELHARDT JF, YANG Y et al.: Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates: toxicity study. Hum. Gene Ther. (1993) 4:771-780.
133. PITT BR, SCHWARZ MA, PILEWSKI JM et al.: Retrovirus-mediated gene transfer in lungs of living fetal sheep. Gene Ther. (1995) 2(5):344-350.
134. KNOWLES MR, PARADISO AM, BOUCHER RC: In vivo nasal potential difference: techniques and protocols for assessing efficacy of gene transfer in cystic fibrosis. Hum. Gene Ther. (1995) 6(4):445-455.
135. BOUCHER RC, KNOWLES MR, JOHNSON LG et al.: Gene therapy for cystic fibrosis using E1-deleted adenovirus: a Phase I trial in the nasal cavity. The University of North Carolina at Chapel Hill. Hum. Gene Ther. (1994) 5:615-639. A dose-effect study was designed to test for safety and efficacy of E1-deleted recombinant adenovirus CFTR vector in CF nasal epithelia.
136. WELSH MJ, SMITH AE, ZABNER J et al.: Cystic fibrosis gene therapy using an adenovirus vector: in vivo safety and efficacy in nasal epithelium. Hum. Gene Ther. (1994) 5:209-219.
137. ZABNER J, COUTURE LA, GREGORY RJ, GRAHAM SM, SMITH AE, WELSH MJ: Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis. Cell (1993) 75:207-216.
138. PORTEOUS DJ, DORIN JR, MCLACHLAN G et al.: Evidence for safety and efficacy of DOTAP cationic liposome mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Ther. (1997) 4(3):210-218.
139. BELLON G, MICHEL-CALEMARD L, THOUVENOT D et al.: Aerosol administration of a recombinant adenovirus expressing CFTR to cystic fibrosis patients: a Phase I clinical trial. Hum. Gene Ther. (1997) 8(1):15-25.
140. ROWNTREE RK, HARRIS A: The phenotypic consequences of CFTR mutations. Ann. Hum. Genet. (2003) 67(Pt 5):471-485.
141. WAGNER JA, MORAN ML, MESSNER AH et al.: A Phase I/II study of tgAAV-CF for the treatment of chronic sinusitis in patients with cystic fibrosis. Hum. Gene Ther. (1998) 9(6):889-909.
142. ALTON EW, STERN M, FARLEY R et al.: Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial. Lancet (1999) 353(9157):947-954.
143. CAPLEN NJ, ALTON EW, MIDDLETON PG et al.: Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis [see comments] [published erratum appears in Nat. Med. (1995) 1(3):272]. Nat. Med. (1995) 1(1):39-46.
144. CAPLEN NJ, ALTON EW, MIDDLETON PG et al.: Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis [see comments] [published erratum appears in Nat. Med (1995) 1(3):272]. Nat. Med. (1995) 1(1):39-46.
145. MIDDLETON PG, CAPLEN NJ, GAO X et al.: Nasal application of the cationic liposome DC-Chol:DOPE does not alter ion transport, lung function or bacterial growth [published erratum appears in Eur. Respir. J. (1994) 7(5):1024]. Eur. Respir. J. (1994) 7(3):442-445.
146. MIDDLETON PG, CAPLEN NJ, GAO X et al.: Nasal application of the cationic liposome DC-Chol:DOPE does not alter ion transport, lung function or bacterial growth [published erratum appears in Eur. Respir. J. (1994) 7(5):1024]. Eur. Respir. J. (1994) 7(3):442-445.
147. ZIADY AG, KELLEY TJ, MILLIKEN E, FERKOL T, DAVIS PB: Functional evidence of CFTR gene transfer in nasal epithelium of cystic fibrosis mice in vivo following luminal application of DNA complexes targeted to the serpin-Enzyme complex receptor. Mol. Ther. (2002) 5(4):413-419. Molecular conjugates that target the serpin enzyme complex were used to compact plasmid DNA containing CFTR cDNA and correct CF murine nasal epithelia.
148. MA T, VETRIVEL L, YANG H et al.: High-affinity activators of cystic fibrosis transmembrane conductance regulator (CFTR) chloride conductance identified by high-throughput screening. J. Biol. Chem. (2002) 277(40):37235-37241. High-throughput screening of 60,000 compounds reveals several activators of CFTR-mediated chloride transport.
149. MA T, THIAGARAJAH JR, YANG H et al.: Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion. J. Clin. Invest. (2002) 110(11):1651-1658. High-throughput screening of 50,000 chemicals uncovers a potent inhibitor of CFTR.
150. http://www.intrabiotics.com/products/index.html Intrabiotics website. Products in development.