Future therapies for cystic fibrosis

Allen, Lucy; Allen, Lorna; Carr, Siobhan B.; Davies, Gwyneth; Downey, Damian; Egan, Marie; Forton, Julian T.; Gray, Robert; Haworth, Charles; Horsley, Alexander; Smyth, Alan R.; Southern, Kevin W.; Davies, Jane C.

Abstract

We are currently witnessing transformative change for people with cystic fibrosis with the introduction of small molecule, mutation-specific drugs capable of restoring function of the defective protein, cystic fibrosis transmembrane conductance regulator (CFTR). However, despite being a single gene disorder, there are multiple cystic fibrosis-causing genetic variants; mutation-specific drugs are not suitable for all genetic variants and also do not correct all the multisystem clinical manifestations of the disease. For many, there will remain a need for improved treatments. Those patients with gene variants responsive to CFTR modulators may have found these therapies to be transformational; research is now focusing on safely reducing the burden of symptom-directed treatment. However, modulators are not available in all parts of the globe, an issue which is further widening existing health inequalities. For patients who are not suitable for- or do not have access to- modulator drugs, alternative approaches are progressing through the trials pipeline. There will be challenges encountered in design and implementation of these trials, for which the established global CF infrastructure is a major advantage. Here, the Cystic Fibrosis National Research Strategy Group of the UK NIHR Respiratory Translational Research Collaboration looks to the future of cystic fibrosis therapies and consider priorities for future research and development.

Citation

Allen, L., Allen, L., Carr, S. B., Davies, G., Downey, D., Egan, M., …Davies, J. C. (2023). Future therapies for cystic fibrosis. Nature Communications, 14(1), Article 693. https://doi.org/10.1038/s41467-023-36244-2

• Journal Article Type: Article
• Acceptance Date: Jan 20, 2023
• Online Publication Date: Feb 8, 2023
• Publication Date: Feb 8, 2023
• Deposit Date: Feb 10, 2023
• Publicly Available Date: Feb 16, 2023
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 1
• Article Number: 693
• DOI: https://doi.org/10.1038/s41467-023-36244-2
• Keywords: General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry; Multidisciplinary
• Public URL: https://nottingham-repository.worktribe.com/output/17087427
• Additional Information: Received: 7 February 2022; Accepted: 20 January 2023; First Online: 8 February 2023; : Lu. Allen, Lo. Allen, J.T.F., and K.W.S. declare no competing interests. S.B.C. has received grants from the NIHR and undertaking consultancy work for Vertex Pharmaceuticals and Chiesi. She has performed advisory roles for Profile Pharma, Pharmaxis and Vertex Pharmaceuticals. Siobhan is the chair of the UK CF registry steering committee and the European CF society patient registry scientific committee. G.D. has performed clinical trial leadership roles and received speaker honoraria from Vertex Pharmaceuticals, and speaker honoraria from Chiesi Ltd for educational events. She holds current grants from UKRI, NIHR and CF Trust. D.D. has received honoraria and/or grants from, Vertex, Proteostasis, Chiesi, Gilead and Insmed. M.E. is a consultant for Xanadu Bio Sciences. R.G. has received speaker fees from Vertex and Chiesi and and provided consultancy work for Chiesi. C.H. has performed clinical trial leadership roles, and educational and/or advisory activities for 30 Technology, Aradigm, Chiesi, CSL Behring, Gilead, Grifols, GSK, Insmed, Janssen, Meiji, Mylan, Novartis, Pneumagen, Shionogi, Teva, Vertex and Zambon. A.H. has performed clinical trial leadership roles, and educational or advisory activities for the following: Boehringer Ingelheim Pharma GmbH, Celtaxys Pharmaceuticals, Flatley Labs, Galapagos NV, Roche-Genentech, Krystal Biotech, Novabiotics, Pulmocide, Vertex Pharmaceuticals. He holds current grants from EPSRC, UKRI, CF Trust, JP Moulton charity, North West Lung Centre Charity. A.R.S. has received research grants; honoraria for lectures; and support for attending meetings from Vertex Pharmaceuticals (all outside the submitted work). A.R.S. has patents issued (Camara M, Williams P, Barrett D, Halliday N, Knox A, Smyth A, Fogarty A, Barr H, Forrester D. Alkyl quinolones as biomarkers of Pseudomonas aeruginosa infection and uses thereof (ExternalRef removed), outside the submitted work. J.C.D. has performed clinical trial leadership roles, and educational and/or advisory activities for the following: Abbvie, Algipharma AS, Bayer AG, Boehringer Ingelheim Pharma GmbH & Co. KG, Eloxx, Enterprise, Galapagos NV, Genentech, ImevaX GmbH, Ionis, LifeArc, Nivalis Therapeutics, Inc., Krystal Biotech, Novartis, PARI Medical Holding GmbH, ProQR Therapeutics III B.V., Proteostasis Therapeutics INC., Pulmocide, Raptor Pharmaceuticals Inc, Recode, Vertex Pharmaceuticals.