Anticipating New Treatments for Cystic Fibrosis: A Global Survey of Researchers.

Bernardo Cabral,Fabio Mota,Carlos Conte Filho,Vito Terlizzi,Onofrio Laselva

doi:10.3390/jcm11051283

Abstract

Cystic fibrosis is a life-threatening disease that affects at least 100,000 people worldwide. It is caused by a defect in the cystic fibrosis transmembrane regulator (CFTR) gene and presently, 360 CFTR-causing mutations have been identified. Since the discovery of the CFTR gene, the expectation of developing treatments that can substantially increase the quality of life or even cure cystic fibrosis patients is growing. Yet, it is still uncertain today which developing treatments will be successful against cystic fibrosis. This study addresses this gap by assessing the opinions of over 524 cystic fibrosis researchers who participated in a global web-based survey. For most respondents, CFTR modulator therapies are the most likely to succeed in treating cystic fibrosis in the next 15 years, especially through the use of CFTR modulator combinations. Most respondents also believe that fixing or replacing the CFTR gene will lead to a cure for cystic fibrosis within 15 years, with CRISPR-Cas9 being the most likely genetic tool for this purpose.

Highlights

Cystic fibrosis (CF) is the most common life-threatening autosomal recessive disease in Caucasian populations, and it is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
The third part consists of a question about which therapeutic option would be most likely to be successful in treating CF: (i) Genetic therapies, (ii) cystic fibrosis transmembrane regulator (CFTR) modulator therapies, or (iii) Other
As mentioned in the Methods section, qualified for the survey, the answers of some knowledge respondents are not included in the results as we chose to report the opinions of the two groups of researchers with greater knowledge on the topic

Summary

Introduction

Cystic fibrosis (CF) is the most common life-threatening autosomal recessive disease in Caucasian populations, and it is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR protein is an ion channel that mediates chloride and bicarbonate transport in the epithelial cells of multiple organs, including the lungs, pancreas, and intestine [6]. The most common mutation that causes CF, c.1521_1523delCTT produces a protein lacking phenylalanine at position 508 (F508del, class II). This mutant CFTR protein exhibits defective processing, mistrafficking, and reduced functional expression as an anion channel at the cell surface, leading to abnormal fluid transport and impaired mucociliary clearance of bacteria—hallmark features of CF lung disease. Pulmonary symptoms are the main cause of reduced quality of life and life expectancy, since they may lead to respiratory insufficiency [8–10]

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