Focus
Prospettive di nuove terapie della fibrosi cistica
NEW THERAPIES OF CYSTIC FIBROSIS
M. Conese, L. Palmieri, E. Copreni
Marzo 2006 - pagg. 155 -173
Abstract
Although to date symptomatic therapies for cystic fibrosis (CF) - based on the eradication/ control of opportunistic infections and facilitation of mucus excretion - have rapidly and significantly increased patients survival, an aetiological therapy is still far from being available. There are several ongoing studies with the aim of correcting the underlying defect of the disease ranging from gene therapy to studies on molecules which will help the mutated CFRT gene to correctly express its protein or to make it work better. Stem cell therapy is a promising technique since it does not require the use of vectors, fundamental in gene therapy. Pharmacogenomics will help developing new drugs and identifying new efficacy indicators of these drugs.
Parole chiave
Classificazione MeSH
Bibliografia
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10. Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002;418: 41-9.
11. Harris RG, Herzog EL, Bruscia EM, Grove JE, Van Arnam JS, Krause DS. Lack of fusion requirement for development of bine marrow-derived epithelia. Science 2004;305: 90-3.
12. Wang G, Bunnell BA, Painter RG, et al. Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: potential therapy for cystic fibrosis. Proc Natl Acad Sci USA 2005;102:186- 91.
13. Loi R, Beckett T, Goncz KK, Suratt BT, Weiss DJ. Limited restoration of cystic fibrosis lung epithelium in vivo with adult marrow derived cells. Am J Respir Crit Care Med 2005; Published on September 22, 2005 as doi:10.1164/rccm.200502-309OC.
14. Coraux C, Nawrocki-Raby B, Hinnrasky J, et al. Embryonic stem cells generate airway epithelial tissue. Am J Respir Cell Mol Biol 2005;32:87-92.
15. Egan ME, Pearson M, Weiner SA, et al. Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 2004; 304:600-2.
16. Song Y, Sonawane ND, Salinas D, et al. Evidence against the rescue of defective ΔF508-CFTR cellular processing by curcumin in cell culture and mouse models. J Biol Chem 2004;279:40629-33.
17. Pedemonte N, Lukacs GL, Du K, et al. Small-molecule correctors of defective ΔF508-CFTR cellular processing identified by high-throughput screening. J Clin Investig 2005;115:2564-71.
18. Lewis HA, Zhao X, Wang C, et al. Impact of the DF508 Mutation in first nucleotide-binding domain of human cystic fibrosis transmembrane conductance regulator on domain folding and structure. J Biol Chem 2005;280:1346-53.
19. Sangiuolo F, D’Apice MR, Gambardella S, Di Daniele N, Novelli G. Toward the pharmacogenomics of cystic fibrosis--an update. Pharmacogenomics 2004;5:861-78.
20. Srivastava M, Eidelman O, Zhang J, et al. Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells. Proc Natl Acad Sci USA 2004;101: 7693-8.
2. Riordan JR, Rommers J, Kerem B, Alon N, Rozmahel R. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 1989;245:1066-73.
3. Rowe SM, Miller S, Sorscher EJ. Cystic Fibrosis. N Engl J Med 2005;352:1992-2001.
4. Colombo C, Bennato V, Costantini D, Castellani S, Conese M. Le nuove terapie per contrastare la fibrosi cistica. Doctor Pediatria 2005;6:8-17.
5. Konstan MW, Davis PB, Wagener JS, et al. Compacted DNA nanoparticles administered to the nasal mucosa of cystic fibrosis subjects are safe and demonstrate partial to complete cystic fibrosis transmembrane regulator reconstitution. Hum Gene Ther 2004; 15:1255-69.
6. Moss RB, Rodman D, Spencer LT, et al. Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial. Chest 2004;125:509-21.
7. Pickles RJ. Physical and biological barriers to viral vector-mediated delivery of genes to the airway epithelium. Proc Am Thorac Soc 2004;1:302-8.
8. Otto WR. Lung epithelial stem cells. J Pathol 2002; 197:527-35.
9. Krause DS, Theise ND, Collector MI, et al. Multiorgan, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001;105:369-77.
10. Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002;418: 41-9.
11. Harris RG, Herzog EL, Bruscia EM, Grove JE, Van Arnam JS, Krause DS. Lack of fusion requirement for development of bine marrow-derived epithelia. Science 2004;305: 90-3.
12. Wang G, Bunnell BA, Painter RG, et al. Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: potential therapy for cystic fibrosis. Proc Natl Acad Sci USA 2005;102:186- 91.
13. Loi R, Beckett T, Goncz KK, Suratt BT, Weiss DJ. Limited restoration of cystic fibrosis lung epithelium in vivo with adult marrow derived cells. Am J Respir Crit Care Med 2005; Published on September 22, 2005 as doi:10.1164/rccm.200502-309OC.
14. Coraux C, Nawrocki-Raby B, Hinnrasky J, et al. Embryonic stem cells generate airway epithelial tissue. Am J Respir Cell Mol Biol 2005;32:87-92.
15. Egan ME, Pearson M, Weiner SA, et al. Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 2004; 304:600-2.
16. Song Y, Sonawane ND, Salinas D, et al. Evidence against the rescue of defective ΔF508-CFTR cellular processing by curcumin in cell culture and mouse models. J Biol Chem 2004;279:40629-33.
17. Pedemonte N, Lukacs GL, Du K, et al. Small-molecule correctors of defective ΔF508-CFTR cellular processing identified by high-throughput screening. J Clin Investig 2005;115:2564-71.
18. Lewis HA, Zhao X, Wang C, et al. Impact of the DF508 Mutation in first nucleotide-binding domain of human cystic fibrosis transmembrane conductance regulator on domain folding and structure. J Biol Chem 2005;280:1346-53.
19. Sangiuolo F, D’Apice MR, Gambardella S, Di Daniele N, Novelli G. Toward the pharmacogenomics of cystic fibrosis--an update. Pharmacogenomics 2004;5:861-78.
20. Srivastava M, Eidelman O, Zhang J, et al. Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells. Proc Natl Acad Sci USA 2004;101: 7693-8.
Corrispondenza: conese.massimo@hsr.it