Novel therapeutic approaches for the management of cystic fibrosis
Keywords:
Cystic fibrosis, CFTR, treatment, infection, gene therapyAbstract
Cystic fibrosis (CF) is a genetic condition characterised by the build-up of thick, sticky mucus that can damage many of the body’s organs. It is a life-long disease that results in a shortened life expectancy, often due to the progression of advanced lung disease. Treatment has previously targeted the downstream symptoms such as diminished mucus clearance and recurrent infection. More recently, significant advances have been made in treating the cause of the disease by targeting the faulty gene responsible. Hope for the development of potential therapies lies with ongoing research into new pharmacological agents and gene therapy. This review gives an overview of CF, and summarises the current evidence regarding the disease management and upcoming strategies aimed at treating or potentially curing this condition.
References
Kreda SM, Davis CW, Rose MC. CFTR, mucins, and mucus obstruction in cystic fibrosis. Cold Spring Harb Perspect Med 2012;2:a009589.
Filkins LM, O'Toole GA. Cystic fibrosis lung infections: Polymicrobial, complex, and hard to treat. PLoS Pathog 2015;11:e1005258.
Lyczak JB, Cannon CL, Pier GB. Lung infections associated with cystic fibrosis. Clin Microbiol Rev 2002;15:194-222.
Keogh RH, Szczesniak R, Taylor-Robinson D, Bilton D. Up-to-date and projected estimates of survival for people with cystic fibrosis using baseline characteristics: A longitudinal study using UK patient registry data. J Cyst Fibros 2018;17:218–27.
European Cystic Fibrosis Society Patient Registry. Database for CF information in 35 participating countries. Available from: https://www.ecfs.eu/ecfspr
US CF Foundation Registry. Annual Reports for detailed information on CF Care and treatment outcomes. Available from: https://www.cff.org/Research/Researcher-Resources/Patient-Registry/
Australian Cystic Fibrosis Data Registry. Annual Reports for Health outcomes and information. Available from: https://www.cysticfibrosis.org.au/dataregistry
Mirtajani SB, Farnia P, Hassanzad M, Ghanavi J, Farnia P, Velayati AA. Geographical distribution of cystic fibrosis; The past 70 years of data analyzis. Biomed Biotech Res J 2017;1:105-12.
ECFS Patient Registry Annual Data Report 2017. PDF Available from: https://www.ecfs.eu/sites/default/files/general-content-images/working-groups/ecfs-patient-registry/ECFSPR_Report2017_v1.3.pdf
Burgel PR, Bellis G, Olesen HV, Viviani L, Zolin A, Blasi F, et al. Future trends in cystic fibrosis demography in 34 European countries. Eur Respir J 2015;46:133-41.
Lao O, Andrés AM, Mateu E, Bertranpetit J, Calafell F. Spatial patterns of cystic fibrosis mutation spectra in European populations. Eur J Hum Genet 2003;11:385-94.
Kosorok MR, Wei WH, Farrell PM. The incidence of cystic fibrosis. Stat Med 1996;15:449-62.
US Cystic Fibrosis Foundation. Registry Annual Data Report 2018. Available from: https://www.cff.org/Research/Researcher-Resources/Patient-Registry/2018-Patient-Registry-Annual-Data-Report.pdf
Davies JC, Geddes DM, Alton EW. Gene therapy for cystic fibrosis. J Gene Med 2001;3:409–17.
Elborn JS. Cystic fibrosis. Lancet 2016;388:2519–31.
Ma J, Zhao J, Drumm ML, Xie J, Davis PB. Function of the R domain in the cystic fibrosis transmembrane conductance regulator chloride channel. J Biol Chem 1997;272:28133‐141.
Tang L, Fatehi M, Linsdell P. Mechanism of direct bicarbonate transport by the CFTR anion channel. J Cyst Fibros 2009;8:115-21.
Ehre C, Ridley C, Thornton DJ. Cystic fibrosis: an inherited disease affecting mucin-producing organs. Int J Biochem Cell Biol 2014;52:136-45.
Mall MA, Hartl D. CFTR: cystic fibrosis and beyond. Eur Respir J 2014;44:1042-054.
Cutting GR. Cystic fibrosis genetics: from molecular understanding to clinical application. Nat Rev Genet 2015;16:45-56.
Tam A, Wadsworth S, Dorscheid D, et al. The airway epithelium: more than just a structural barrier. Ther Adv Respir Dis 2011;5:255-73.
Montoro DT, Haber AL, Biton M, Vinarsky V, Lin B, Birket SE, et al. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 2018;560:319-324.
Moore PJ, Tarran R. The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis lung disease. Expert Opin Ther Targets 2018;22:687-701.
Saint-Criq V, Gray MA. Role of CFTR in epithelial physiology. Cell Mol Life Sci 2017;74:93-115.
Derichs N, Jin BJ, Song Y, et al. Hyperviscous airway periciliary and mucous liquid layers in cystic fibrosis measured by confocal fluorescence photobleaching. FASEB J 2011;25:2325-32.
Haq IJ, Gray MA, Garnett JP, Ward C, Brodli M. Airway surface liquid homeostasis in cystic fibrosis: pathophysiology and therapeutic targets. Thorax 2016;71:284-7.
Hanukoglu I, Boggula VR, Vaknine H, Sharma S, Kleyman T, Hanukoglu A. Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages. Histochem Cell Biol 2017;147:733-48.
Al Sinani S, Al-Mulaabed S, Al Naamani K, Sultan R. Cystic fibrosis liver disease: Know more. Oman Med J 2019;34:482-9.
de Souza DAS, Faucz FR, Pereira‐Ferrari L, Sotomaior VS, Raskin Sl. Congenital bilateral absence of the vas deferens as an atypical form of cystic fibrosis: Reproductive implications and genetic counseling. Andrology 2018;6:127-35.
Cystic Fibrosis Mutation Database Statistics [Internet]. CFMDB statistics. Accessed: October 2020. Available from: http://www.genet.sickkids.on.ca/StatisticsPage.html
Karimi N, Pour AB, Alibakhshi R, Almasi S. Haplotype analysis of the CFTR gene on normal and mutant CFTR genes. Mutat Res 2020;821:111708
Castellani C, Cuppens H, Macek M Jr, Cassiman JJ, Kerem E, Durie P, et al. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J Cyst Fibros 2008;7:179‐96.
Fraser-Pitt D, O’Neil D. Cystic fibrosis-a multiorgan protein misfolding disease. Future Sci OA 2015;1:FSO57.
Castellani C, Massie J. Newborn screening and carrier screening for cystic fibrosis: alternative or complementary? Eur Respir J 2014;43:20-3.
Farrell PM, Rosenstein BJ, White TB, Accurso FJ, Castellani C, Cutting GR, et al. Guidelines for diagnosis of cystic fibrosis in newborn through older adults: Cystic Fibrosis Foundation Report. J Pediatr 2008;153:S4-14.
Mishra A, Greaves R, Massie J. The relevance of sweat testing for the diagnosis of cystic fibrosis in the genomic era. Clin Biochem Rev 2005;26:135–53.
Shaw J, Scotchman E, Chandler N, et al. PREIMPLANTATION GENETIC TESTING: Non-invasive prenatal testing for aneuploidy, copy-number variants and single-gene disorders. Reproduction 2020;160:A1-A11.
Rowe SM, Clancy JP, Wilschanski M. Nasal potential difference measurements to assess CFTR ion channel activity. Methods Mol Biol 2011;741:69-86.
Long JM, Fauset‐Jones J, Dixon MJ, Worthington-Riley D, Sharma V, Patel L, et al. Annual review hospital visits for patients with cystic fibrosis. J R Soc Med 2001;94(s40):S12–6.
Kamal N, Surana P, Koh C. Liver disease in patients with cystic fibrosis. Curr Opin Gastroenterol 2018;34:146-51.
Bishay L, Sawicki G. Strategies to optimize treatment adherence in adolescent patients with cystic fibrosis. Adolesc Health Med Ther 2016;7:117-24.
McVean RJ, Orr A, Webb AK, et al. Treatment of urinary incontinence in cystic fibrosis. J Cyst Fibros 2003;2:171-6.
Agent P, Parrott H. Inhaled therapy in cystic fibrosis: agents, devices and regimens. Breathe (Sheff) 2015;11:110-8.
Scherer TA, Spengler CM, Owassapian D, Imhof E, Buotellier U. Respiratory muscle endurance training in chronic obstructive pulmonary disease: impact on exercise capacity, dyspnea, and quality of life. Am J Respir Crit Care Med 2000;162:1709-14.
Button BM, Button B. Structure and function of the mucus clearance system of the lung. Cold Spring Harb Perspect Med 2013;3:a009720.
Mauch RM, Kmit AH, Marson FA, Levy CE, Barros-Filho A, Ribeiro JD. Association of growth and nutritional parameters with pulmonary function in cystic fibrosis: a literature review. Rev Paul Pediatr 2016;34:503‐9.
Lai HJ, Shoff SM. Classification of malnutrition in cystic fibrosis: implications for evaluating and benchmarking clinical practice performance. Am J Clin Nutr 2008;88:161-6.
Cohen-Cymberknoh M, Shoseyov D, Kerem E. Managing cystic fibrosis: strategies that increase life expectancy and improve quality of life. Am J Respir Crit Care Med 2011;183:1463-71.
Parsons HG, Beaudry P, Dumas A, Pencharz PB. Energy needs and growth in children with cystic fibrosis. J Pediatr Gastroenterol Nutr 1983;2:44-9.
Quittner AL, Goldbeck L, Abbott J, Duff A, Lambrecht P, Solé A, et al. Prevalence of depression and anxiety in patients with cystic fibrosis and parent caregivers: Results of The International Depression Epidemiological Study across nine countries. Thorax 2014;69:1090-7.
Quittner AL, Abbott J, Georgiopoulos AM, Goldbeck L, Smith B, Hempstead SE, et al. International Committee on mental health in cystic Fibrosis: Cystic fibrosis Foundation and European cystic fibrosis Society consensus statements for screening and treating depression and anxiety. Thorax 2016;71:26-34.
Martin A, Rief W, Klaiberg A, Braehler E. Validity of the brief patient health questionnaire mood scale (PHQ-9) in the general population. Gen Hosp Psychiatry 2006;28:71–7.
Dierker LC, Albano AM, Clarke GN, Heimberg RG, Kendall PC, Merikangas KR, et al. Screening for anxiety and depression in early adolescence. J Am Acad Child Adolesc Psychiatry 2001;40:929-36.
Eisenberg D, Gollust SE, Golberstein E, Hefner JL. Prevalence and correlates of depression, anxiety, and suicidality among university students. Am J Orthopsychiatry 2007;77:534-42.
National Institute for Health and Care Excellence (NICE). Cystic fibrosis: diagnosis and management – NICE guideline [NG78]. Available from: https://www.nice.org.uk/guidance/ng78/chapter/recommendations
Elkins MR, Bye PT. Mechanisms and applications of hypertonic saline. J R Soc Med 2011;104:S2-5.
Ratjen F, Davis SD, Stanojevic S, Kronmal RA, Hinckley Stukovsky KD, Jorgensen N, et al. Inhaled hypertonic saline in preschool children with cystic fibrosis (SHIP): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2019;7:802-9.
Pressler T. Review of recombinant human deoxyribonuclease (rhDNase) in the management of patients with cystic fibrosis. Biol Targets Ther 2008;2:611.
Suri R, Metcalfe C, Lees B, Grieve R, Flather M, Normand C, et al. Comparison of hypertonic saline and alternate-day or daily recombinant human deoxyribonuclease in children with cystic fibrosis: a randomised trial. Lancet 2001;358:1316-21.
Suri R, Grieve R, Normand C, Metcalfe C, Thompson S, Wallis C, Bush A. Effects of hypertonic saline, alternate day and daily rhDNase on healthcare use, costs and outcomes in children with cystic fibrosis. Thorax 2002;57:841‐6.
King M, Dasgupta B, Tomkiewicz RP, Brown NE. Rheology of cystic fibrosis sputum after in vitro treatment with hypertonic saline alone and in combination with recombinant human deoxyribonuclease I. Am J Respir Crit Care Med 1997;156:173-7.
Flume PA, Aitken ML, Bilton D, Agent P, Charlton B, Forster E, et al. Optimising inhaled mannitol for cystic fibrosis in an adult population. Breathe Sheff Engl 2015;11:39-48.
Trapnell BC. Inhaled dry powder mannitol: a solution for cystic fibrosis. Am J Respir Crit Care Med 2012;185:596-8.
Moss RB, Flume PA, Elborn JS, Cooke J, Rowe SM, McColley SA, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an arg117his-CFTR mutation: a double-blind, randomised controlled trial. Lancet Respir Med 2015;3:524-33.
De Boeck K, Munck A, Walker S, Faro A, Hiatt P, Gilmartin G, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. J Cyst Fibros 2014;13:674-80.
Davies JC, Wainwright CE, Canny GJ, Chilvers MA, Howenstine MS, Munck A, 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;187:1219-25.
McKone EF, Borowitz D, Devinek P, Griese M, Konstan MW, Wainwright C, et al. Long-term safety and efficacy of ivacaftor in patients with cystic fibrosis who have the Gly551Asp-CFTR mutation: a phase 3, open-label extension study (PERSIST). Lancet Respir Med 2014;2:902-10.
Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011;365:1663-72.
McNamara JJ, McColley SA, Marigowda G, Liu F, Tian S, Owen CA, et al. Safety, pharmacokinetics and pharmacodynamics of lumacaftor and ivacaftor combination therapy in children aged 2-5 years with cystic fibrosis homozygous for F508del-CFTR: ah open-label phase 3 study. Lancet Respir Med 2019;7:325-35.
Milla CE, Ratjen F, Marigowda G, Liu F, Waltz D, Rosenfeld M, et al. Lumacaftor/ivacaftor in patients aged 6-11 years with cystic fibrosis and homozygous for F508del-CFTR. Am J Respir Crit Care Med 2017;195:912-20.
Taylor-Cousar JL, Jain M, Barto TL, Haddad T, Atkinson J, Tian S, et al. Lumacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease homozygous for F508del-CFTR. J Cyst Fibros 2018;17:228-35.
Elborn JS, Ramsey BW, Boyle MP, Konstan MW, Huang W, Marigowda G, et al. Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for phe508del CFTR by pulmonary function subgroup: a pooled analysis. Lancet Respir Med 2016;4:617-26.
Ratjen F, Hug C, Marigowda G, Tian S, Huang X, Stanojevic S, et al. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6-11 with cystic fibrosis homozygous for F508del-CFTR: a randomized, placebo-controlled phase 3 trial. Lancet Respir Med 2017;5:557-67.
Konstan MW, McKone EF, Moss RB, Marigowda G, Tian S, Waltz D, et al. Assessment of safety and efficacy of long‐term treatment with combination lumacaftor and ivacaftor therapy in patients with cystic fibrosis homozygous for the F508del‐CFTR mutation (PROGRESS): a phase 3, extension study. Lancet Res Med 2017;5:107‐18.
Walker S, Glume P, McNamara J, Solomon M, Chilvers M, Chmiel J, et al. A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 through 11 years with cystic fibrosis. J Cyst Fibros 2019:18:708-13.
Taylor-Cousar JL, Munck A, McKone EF, van der Ent CK, Moeller A, Simard C, et al. Tezacaftor-Ivacaftor in patients with cystic fibrosis homozygous for Phe508del. N Eng J Med 2017;377:2013-23.
Rowe SM, Daines C, Ringshausen FC, Kerem E, Wilson J, Tullis E, et al. Tezacaftor-Ivacaftor in residual-function heterozygotes with cystic fibrosis. N Eng J Med 2017;377:2024-34.
Middleton PG, Mall MA, Drevínek P, Lands LC, McKone EF, Polineni D, et al. Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single phe508del allele. N Eng J Med 2019;381:1809-19.
Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet 2019;394:1940-8.
Csanády L, Töröcsik B. Cystic fibrosis drug ivacaftor stimulates CFTR channels at picomolar concentrations. Elife 2019;8:e46450.
Guigui S, Wang J, Cohen RI. The use of ivacaftor in CFTR mutations resulting in residual functioning protein. Resp Med Case Rep 2016;19:193‐5.
Carlile GW, Yang Q, Matthes E, Liao J, Radinovic S, Miyamoto, et al. A novel triple combination of pharmacological chaperones improves F508del-CFTR correction. Sci Rep 2018;8:11404.
Clancy JP. Rapid therapeutic advances in CFTR modulator science. Pediatr Pulmonol 2018;53:S4-11.
Ridley K, Condren M. Elexacaftor-Tezacaftor-Ivacaftor: The first triple-combination cystic fibrosis transmembrane conductance regulator modulating therapy. J Pediatr Pharmacol Ther 2020;25:192-7.
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Cystic Fibrosis Agents. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547889/
Chaudary N. Triplet CFTR modulators: future prospects for treatment of cystic fibrosis. Ther Clin Risk Manag 2018;14:2375-2383.
Vertex Pharmaceuticals, Inc. Kalydeco [Product Monograph] 2012. Laval, Quebec: Available from: https://pi.vrtx.com/files/uspi_ivacaftor.pdf
Vertex Pharmaceuticals, Inc. Orkambi [Product Monograph] 2015. Laval, Quebec: Available from: https://pi.vrtx.com/files/uspi_lumacaftor_ivacaftor.pdf
Vertex Pharmaceuticals, Inc. Symdeko [Product Monograph] 2018. Laval, Quebec: Available from: https://pi.vrtx.com/files/uspi_tezacaftor_ivacaftor.pdf
Vertex Pharmaceuticals, Inc. Trikafta [Product Monograph] 2019. Laval, Quebec: Available from: https://pi.vrtx.com/files/uspi_elexacaftor_tezacaftor_ivacaftor.pdf
European Medicine Agency. Pending EC decision for Ivacaftor – Committee for Medicinal Products for Human Use (CHMP). Available from: https://www.ema.europa.eu/en/medicines/human/summaries-opinion/kalydeco-3#key-facts-section
European Medicine Agency. Pending EC decision for Symkevi – Committee for Medicinal Products for Human Use (CHMP). Available from: https://www.ema.europa.eu/en/medicines/human/summaries-opinion/symkevi-0
Flume PA, O’Sullivan BP, Robinson KA, Goss CH, Mogayzel PJ Jr, Willey-Courand B, et al. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2007;176:957-69.
De Rose V, Molloy K, Gohy S, Pilette C, Greene CM. Airway epithelium dysfunction in cystic fibrosis and COPD. Mediators Inflamm 2018;2018:1309746.
Balfour-Lynn IM, Elborn JS. "CF asthma": what is it and what do we do about it? Thorax 2002;57:742-8.
Dahl M, Tybjærg-Hansen A, Lange P, Nordestgaard BG. DeltaF508 heterozygosity in cystic fibrosis and susceptibility to asthma. Lancet 1998;351:1911-3. Erratum in Lancet 1998;352:1230.
Schroeder SA, Gaughan DM, Swift M. Protection against bronchial asthma by CFTR delta F508 mutation: a heterozygote advantage in cystic fibrosis. Nat Med 1995;1:703-5.
Halfhide C, Evans HJ, Couriel J. Inhaled bronchodilators for cystic fibrosis. Cochrane Database Syst Rev 2005:CD003428.
Smith S, Edwards CT. Long-acting inhaled bronchodilators for cystic fibrosis. Cochrane Database Syst Rev 2017:CD012102.
Barry PJ, Flume PA. Bronchodilators in cystic fibrosis: a critical analysis. Expert Rev Respir Med 2017;11:13-20.
Eckrich J, Zissler UM, Serve F, Leutz P, Smaczny C, Schmitt-Grohé S, et al. Airway inflammation in mild cystic fibrosis. J Cyst Fibros 2017;16:107-15.
Konstantinos Katsoulis K, Kostikas K, Kontakiotis T. Techniques for assessing small airways function: Possible applications in asthma and COPD. Respir Med 2016;119:e2-9.
Scichilone N, Contoli M, Paleari D, Pirina P, Rossi A, Sanguinetti CM, et al. Assessing and accessing the small airways; implications for asthma management. Pulm Pharmacol Ther 2013;26:172-9.
Balfour-Lynn IM, Welch K. Inhaled corticosteroids for cystic fibrosis. Cochrane Database Syst Rev 2016:CD001915.
De Boeck K, De Baets F, Malfroot A, Desager K, Mouchet F, Proesmans M. Do inhaled corticosteroids impair long-term growth in prepubertal cystic fibrosis patients? Eur J Pediatr 2007;166:23-8.
Latorre M, Novelli F, Vagaggini B, Braido F, Papi A, Sanduzzi A, et al. Differences in the efficacy and safety among inhaled corticosteroids (ICS)/long-acting beta2-agonists (LABA) combinations in the treatment of chronic obstructive pulmonary disease (COPD): Role of ICS. Pulm Pharmacol Ther 2015;30:44-50.
Lynch JP III, Sayah DM, Belperio JA, Weigt SS. Lung transplantation for cystic fibrosis: results, indications, complications, and controversies. Semin Respir Crit Care Med 2015;36:299-320.
Meachery G, De Soyza A, Nicholson A, Parry G, Hasan A, Tocewicz K, et al. Outcomes of lung transplantation for cystic fibrosis in a large UK cohort. Thorax 2008;63:725-31.
Davies JC, Alton EWF, Bush A. Cystic fibrosis. BMJ 2007;335:1255-9.
Coburn B, Wang PW, Diaz Caballero J, Clark ST, Brahma V, Donaldson S, et al. Lung microbiota across age and disease stage in cystic fibrosis. Sci Rep 2015;5:10241.
Huang YJ, LiPuma JJ. The microbiome in cystic fibrosis. Clin Chest Med 2016;37:59-67.
Bhagirath AY, Li Y, Somayajula D, Dadashi M, Badr S, Duan K. Cystic fibrosis lung environment and Pseudomonas aeruginosa infection. BMC Pulm Med 2016;16:174.
Coutinho HDM, Falcao-Silva VS, Goncalves GF. Pulmonary bacterial pathogens in cystic fibrosis patients and antibiotic therapy: a tool for the health workers. Int Arch Med 2008;1:24.
Brooke JS. Stenotrophomonas maltophilia: An emerging global opportunistic pathogen. Clin Microbiol Rev 2012;25:2–41.
Tamma PD, Cosgrove SE, Maragakis LL. Combination therapy for treatment of infections with gram-negative bacteria. Clin Microbiol Rev 2012;25:450-70.
Peloquin CA, Berning SE, Nitta AT, Simone PM, Goble M, Huitt GA, et al. Aminoglycoside toxicity: daily versus thrice-weekly dosing for treatment of mycobacterial diseases. Clin Infect Dis 2004;38:1538-44.
Petkova M, Gesson C, De Vos S, Conrath K, Corveleyn S, Geller D, et al. safety, tolerability and pharmacokinetics of a novel CFTR potentiator GLPG3067 in healthy volunteers. Galapagos Biotech 2017 Poster. Available at: https://www.glpg.com/docs/view/59fc5ef4102ec-en
Singh AK, Fan Y, Balut C, Alani S, Manelli AM, Swenses AM, et al. Biological characterization of F508delCFTR protein processing by the CFTR corrector ABBV-2222/GLPG2222. J Pharmacol Exp Ther 2020;372:107-18.
Lopes-Pacheco M. CFTR modulators: The changing face of cystic fibrosis in the era of precision medicine. Front Pharmacol 2020;10:1662.
Proteostasis Therapeautics, Inc. Recent positive phase 2 and ex vivo organoid study data support initiation of MORE and CHOICES trials in 2020 proteostatis therapeutics regulatory update 2020. Available from: https://www.prnewswire.com/news-releases/proteostasis-therapeutics-regulatory-update-following-scientific-advice-meeting-with-mhra-300985498.html
Molinski SV, Ahmadi S, Ip W, Ouyang H, Villella A, Miller JP, et al. Orkambi® and amplifier co-therapy improves function from a rare CFTR mutation in gene-edited cells and patient tissue. EMBO Mol Med 2017;9:1224-43.
Matos AM, Matos P. Combination therapy in Phe508del CFTR: how many will be enough? J Lung Health Dis 2018;2:9-16.
Dabrowski M, Bukowy-Bieryllo Z, Zietkiewicz E. Advances in therapeutic use of a drug-stimulated translational readthrough of premature termination codons. Mol Med 2018;24:25.
Wilschanski M. Class 1 CF Mutations. Front Pharmacol 2012;3:117.
Mercuri E, Muntoni F, Osorio AN, Tulinius M, Buccella F, Morgenroth LP, et al. Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study. J Comp Eff Res 2020;9:341-60.
Abidi NZ, Haq IJ, Gardner AI, Brodlie M. Ataluren in cystic fibrosis: development, clinical studies and where are we now? Expert Opin Pharmacother2017;18:1363-71.
Aslam AA, Higgins C, Sinha IP, et al. Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis. Cochrane Database Systc Rev2017;1:CD012040. rawford DK, Alroy I, Sharpe N, Goddeeris MM, Williams G. Premature versus native stop codon read-through by ELX-02. J Pharmacol Exp Ther 2020;374:264-72.
Moore PJ, Robert Tarran R. The epithelial sodium channel (ENaC) as a therapeutic target for cystic fibrosis lung disease. Expert Opin Ther Targets 2018;22:8:687-701.
Mall MA. ENaC inhibition in cystic fibrosis: potential role in the new era of CFTR modulator therapies. Eur Respir J 2020;2000946.
Reihill JA, Walker B, Hamilton RA, et al. Inhibition of protease-epithelial sodium channel signaling improves mucociliary function in cystic fibrosis airways. Am J Respir Crit Care Med 2016;194:701-10.
Rowe SM, Reeves G, Hathorne H, Solomon GM, Abbi S, Renard D, et al. Reduced sodium transport with nasal administration of the prostasin inhibitor camostat in subjects with cystic fibrosis. Chest 2013;144:200-7.
Strug LJ, Stephenson AL, Panjwani N, Harris A. Recent advances in developing therapeutics for cystic fibrosis. Hum Molr Genet 2018;27:R173–86.
Hobbs CA, Blanchard MG, Alijevic O, Da Tan C, Kellenberge S, Bencharit S, et al. Identification of the SPLUNC1 ENaC-inhibitory domain yields novel strategies to treat sodium hyperabsorption in cystic fibrosis airway epithelial cultures. Am J Physiol Lung Cell Mol Physiol 2014;1;306:L708.
Lennox A, Myerburg MM. SPX-101 is a promising and novel nebulized ENaC inhibitor. Am J Respir Crit Care Med 2017;196:671-2.
Scott DW, Walker MP, Sesma J, Wu B, Stuhlmiller TJ, Sabater JR, et al. SPX-101 is a novel epithelial sodium channel-targeted therapeutic for cystic fibrosis that restores mucus transport. Am J Respir Crit Care Med 2017;196:734-44.
Couroux P, Farias P, Rizvi L, Griffin K, Hudson C, Crowder T, et al. First clinical trials of novel ENaC targeting therapy, SPX-101, in healthy volunteers and adults with cystic fibrosis. Pulm Pharmacol Ther 2019;58:101819.
Cystic Fibrosis Foundation. Drug Development Pipeline: SPX-101. . Available from: https://www.cff.org/Trials/Pipeline/details/10128/SPX-101
Crosby JR, Zhao C, Jiang C, Bai D, Katz M, Greenlee S, et al. Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice. J Cyst Fibros 2017;16:671-80.
Ionis Pharmaceuticals, Inc. Ionis' inhaled antisense medicine demonstrates potential as a novel treatment for cystic fibrosis. Ionis Pharmaceuticals, Inc. Update 2020. Available from: https://ir.ionispharma.com/news-releases/news-release-details/c-o-r-r-e-c-t-i-o-n-ionis-pharmaceuticals-inc-0
Manunta MDI, Tagalakis AD, Attwood M, Aldossary AM, Barnes JL, Munye MM, et al. Delivery of ENaC siRNA to epithelial cells mediated by a targeted nanocomplex: a therapeutic strategy for cystic fibrosis. Sci Rep 2017;7:700.
Burney TJ, Davies JC. Gene therapy for the treatment of cystic fibrosis. Appl Clin Genet 2012;5:29-36.
Karda R, Buckley SMK, Waddington SN. Gene therapy with adeno-associated virus for cystic fibrosis. Am J Respir Crit Care Med 2016;193:234–6.
Donnelley M, Parsons DW. Gene therapy for cystic fibrosis lung disease: overcoming the barriers to translation to the clinic. Front Pharmacol 2018;9,1381.
Griesenbach U, Inoue M, Hasegawa M, Alton EWFW. Viral vectors for cystic fibrosis gene therapy: What does the future hold? Dove Press 2010;2:159-71.
Naldini L, Blomer U, Gage FH, Trono D, Verma IM. Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci USA 1996;93:11382-8.
Griesenbach U, Inoue M, Meng C, Farley R, Chan M, Newman NK, et al. Assessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for lung gene therapy. Am J Respir Crit Care Med 2012;186,846-56.
Moradali MF, Ghods S, Rehm BH. Pseudomonas aeruginosa lifestyle: a paradigm for adaptation, survival, and persistence. Front Cell Infect Microbiol 2017;7:39.
Alton E, Armstrong DK, Ashby D, Bayfield KJ, Bilton D, Bloomfield EVm et al. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med 2015;3-:684–91.
Lai SK, Wang YY, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 2009;61:158-71.
Suk JS, Lai SK, Boylan NJ, Dawson MR, Boyle MP, Hanes J. Rapid transport of muco-inert nanoparticles in cystic fibrosis sputum treated with N-acetyl cysteine. Nanomedicine (Lond) 2011;6:365-75.
Lababidi N, Sigal V, Koenneke A, Schwarzkopf K, Manz A, Schneider M . Microfluidics as tool to prepare size-tunable PLGA nanoparticles with high curcumin encapsulation for efficient mucus penetration. Beilstein J Nanotechnol 2019;10:2280-2293.
Ong V, Mei V, Cao L, Lee K, Chung EJ. Nanomedicine for cystic fibrosis. SLAS Technol 2019;24:169-80.
Velino C, Carella F, Adamiano A, Sanguinetti N, Vitali A, Catalucci D, et al. Nanomedicine approaches for the pulmonary treatment of cystic fibrosis. Front Bioeng Biotechnol 2019;7:406.
Sahu I, Haque AKMA, Weidensee B, Weinmann P, Kormann MSD. Recent developments in mRNA-based protein supplementation therapy to target lung diseases. Mol Ther 2019;27:803-23.
Translate Bio, Inc. Translate Bio announces interim results from phase 1/2 clinical trial of MRT5005 in patients with cystic fibrosis, 2019. Available from: http://investors.translate.bio/node/7101/pdf
Marangi M, Pistritto G. Innovative therapeutic strategies for cystic fibrosis: moving forward to CRISPR technique. Front Pharmacol 2018;9:396.
Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR‐Cas9 for genome engineering. Cell 2014;157:1262‐-78.
Hille F, Charpentier E. CRISPR-Cas: biology, mechanisms and relevance. Philos Trans R Soc Lond B Biol Sci 2016;371:20150496.
Hodges CA, Conlon RA. Delivering on the promise of gene editing for cystic fibrosis. Genes Dis 2019;6:97–108.
Suzuki S, Chosa K, Lee A, Yezzi M, Kai H, Gruenert D. Seamless correction by donor DNA of a class I CFTR mutation facilitated by a double nicking CRISPR/Cas9 in CF-iPSCs. Mol Therapy 2016;24:S51
Park J, Bae S. Cpf1-database: web-based genome-wide guide RNA library design for gene knockout screens using CRISPR-Cpf1. Bioinformatics 2017;34:1077-79.
Ledford H. Alternative CRISPR system could improve genome editing. Nature 2015;526:17.
Zhang Y, Long C, Li H, McAnally JR, Baskin KK, Shelton JM et al. CRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice. Sci Adv 2017;3:e1602814.
Maule G, Casini A, Montagna C, Ramalho AS, De Boeck K, Debyser Z, et al. Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing. Nat Commun 2019;10:3556. Author Correction in: Nat Commun 2020;11:5457.
Katz MG, Fargnoli AS, Bridges CR. Myocardial gene transfer: routes and devices for regulation of transgene expression by modulation of cellular permeability. Hum Gene Ther 2013;24:375-92.
Published
Issue
Section
License
Mattioli 1885 has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
How to Cite
