Biological Sciences Faculty, University Complutense of Madrid, C/ José Antonio Nováis 2, 28040, Madrid, Spain.
National Museum of Natural Sciences-Superior Council of Scientific Investigations, C/ José Gutiérrez Abascal 2, 28006, Madrid, Spain.
Med Biol Eng Comput. 2019 Feb;57(2):413-425. doi: 10.1007/s11517-018-1885-1. Epub 2018 Sep 1.
Cystic fibrosis is an inherited disorder of the cystic fibrosis transmembrane conductance regulator gene (CFTR) that affects the respiratory system. Current treatment is palliative, but there is a gene therapy under investigation which involves inserting a functional CFTR gene into affected cells. Given the clinical variety of the disease, it is necessary to characterize key indicators in its evolution (e.g., the number of functional alveolar sacs and its relationship with a healthy lung function), to anticipate its advancement. A dynamic model was used to evaluate the evolution of cystic fibrosis over time. We considered the application of conventional medical treatments and evaluated the benefits of the application of an experimental gene therapy that would reverse lung damage. Without treatment the life expectancy of the patient is low, but it is increased with the application of conventional treatments, being the progressive loss of the lung function inevitable. Simulating the application of a gene therapy, the life expectancy of patients would not be limited, given the recovery of all altered cellular processes. With this model we can make predictions that demonstrate the need for a curative treatment, in addition to presenting the evolution of pathology in a specific clinical setting. Graphical abstract Graphic representation of the analysis performed in the present work on simulation of different clinical situations regarding patients with cystic fibrosis of pulmonary involvement.
囊性纤维化是一种由囊性纤维化跨膜电导调节基因 (CFTR) 引起的遗传性疾病，会影响呼吸系统。目前的治疗方法是姑息性的，但有一项正在研究的基因治疗方法涉及将功能性 CFTR 基因插入受影响的细胞。鉴于该疾病的临床表现多样，有必要对其演变过程中的关键指标进行特征描述（例如，功能性肺泡囊的数量及其与健康肺功能的关系），以预测其进展。我们使用动态模型来评估囊性纤维化随时间的演变。我们考虑了常规医疗治疗的应用，并评估了应用实验性基因治疗逆转肺损伤的益处。如果不治疗，患者的预期寿命很短，但通过应用常规治疗可以延长，而肺功能的逐渐丧失是不可避免的。模拟基因治疗的应用，患者的预期寿命将不会受到限制，因为所有改变的细胞过程都得到了恢复。通过该模型，我们可以做出预测，证明除了在特定临床环境中展示病理学的演变之外，还需要一种治愈性的治疗方法。
