Future therapies for cystic fibrosis.
Future therapies for cystic fibrosis.
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DOI：
10.1038/s41467-023-36244-2
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发表时间：
2023-02-08
影响因子：
16.6
通讯作者：
Davies, Jane C.
中科院分区：
文献类型：
--
作者：
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.
目前，我们正在见证囊性纤维化患者的革命性变化，因为引入了小分子、突变特异性药物，能够恢复有缺陷的蛋白质、囊性纤维化跨膜电导调节剂 (CFTR) 的功能。然而，尽管是一种单基因疾病，但存在多种导致囊性纤维化的遗传变异；突变特异性药物并不适合所有基因变异，也不能纠正该疾病的所有多系统临床表现。对于许多人来说，仍然需要改进的治疗方法。那些携带对 CFTR 调节剂有反应的基因变异的患者可能已经发现这些疗法具有变革性；目前研究的重点是安全地减轻针对症状的治疗的负担。然而，调节剂并非在全球所有地区都可用，这一问题进一步扩大了现有的健康不平等。对于不适合或无法获得调节药物的患者，替代方法正在试验中取得进展。这些试验的设计和实施将会遇到挑战，而已建立的全球 CF 基础设施是一个主要优势。英国 NIHR 呼吸转化研究合作组织的囊性纤维化国家研究战略小组在此展望囊性纤维化治疗的未来，并考虑未来研究和开发的优先事项。在过去的几十年里，囊性纤维化的情况发生了巨大的变化，患者的生活质量、预后和预测生存率均得到改善。在某种程度上，这与新型 CFTR 调节药物的可用性有关，尽管之前在针对症状的治疗和诊断方面的进展已经带来了实质性的改进。然而，作为国家 CF 重点小组的一部分，作者们认识到还需要做更多的工作，并从这个角度概述了他们对研究重点的考虑。
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. The cystic fibrosis landscape has changed dramatically over the last few decades, with improvements in patient quality of life, prognosis and predicted survival. In part, this is related to the availability of novel CFTR modulator drugs, although prior advances in symptom-directed therapies and diagnosis had already led to substantial improvements. However, the authors, part of a national CF focused group, recognize that more needs to be done and outline their considerations on research priorities in this perspective.
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DOI：
10.1164/rccm.200911-1646oc
发表时间：
2011-03-15
影响因子：
24.7
作者：
Aurora, Paul;Stanojevic, Sanja;Stocks, Janet
通讯作者：
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影响因子：
5.2
作者：
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DOI：
10.1038/nrg3849
发表时间：
2015-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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影响因子：
5.2
作者：
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通讯作者：
Lee, Tim
DOI：
10.1016/j.jcf.2020.09.011
发表时间：
2021-07
期刊：
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
影响因子：
--
作者：
Baker E;Harris WT;Rowe SM;Rutland SB;Oates GR
通讯作者：
Oates GR