Univ Brest, Inserm, EFS, UMR 1078, 22 Avenue Camille Desmoulins, F-29200 Brest, France.
Int J Mol Sci. 2024 Sep 4;25(17):9599. doi: 10.3390/ijms25179599.
Just over thirty years is the span of a generation. It is also the time that has passed since the discovery of the gene responsible for cystic fibrosis. Today, it is safe to say that this discovery has revolutionized our understanding, research perspectives, and management of this disease, which was, thirty years ago, a pediatric condition with a grim prognosis. The aim of this review is to present the advances that science and medicine have brought to our understanding of the pathophysiology of the disease and its management, which in many ways, epitomizes modern molecular genetic research. Since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989, modeling the CFTR protein, deciphering its function as an ion channel, and identifying its molecular partners have led to numerous therapeutic advances. The most significant advancement in this field has been the discovery of protein modulators that can target its membrane localization and chloride channel activity. However, further progress is needed to ensure that all patients can benefit from a therapy tailored to their mutations, with the primary challenge being the development of treatments for mutations leading to a complete absence of the protein. The present review delves into the history of the multifaceted world of CF, covering main historical facts, current landscape, clinical management, emerging therapies, patient perspectives, and the importance of ongoing research, bridging science and medicine in the fight against the disease.
三十年多一点的时间是一代人的跨度。也是发现导致囊性纤维化的基因的时间。今天，可以肯定地说，这一发现彻底改变了我们对这种疾病的理解、研究视角和管理，三十年前，这种疾病还是一种预后严峻的儿科疾病。本篇综述的目的是介绍科学和医学在理解疾病的病理生理学及其管理方面带来的进展，这在许多方面都体现了现代分子遗传研究。自 1989 年发现囊性纤维化跨膜电导调节因子 (CFTR) 基因以来，对 CFTR 蛋白进行建模、揭示其作为离子通道的功能以及确定其分子伴侣，已经带来了许多治疗进展。该领域最重要的进展是发现了可以靶向其膜定位和氯离子通道活性的蛋白调节剂。然而，仍需要进一步的进展来确保所有患者都能从针对其突变的治疗中受益，主要挑战是为导致蛋白完全缺失的突变开发治疗方法。本综述深入探讨了囊性纤维化这一多方面世界的历史，涵盖了主要的历史事实、当前的现状、临床管理、新兴疗法、患者视角以及正在进行的研究的重要性，将科学和医学结合起来，共同对抗这种疾病。
