Cystic fibrosis: current treatment and future direction

Abstract

Cystic fibrosis is an autosomal recessive genetic disorder, characterized by mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to abnormality in the chloride channels of the mucus and sweat producing glands. Multiple organs systems are affected in this disorder, like respiratory system and gastrointestinal tract, severely impacting the patient’s quality of life, eventually leading on to several complications and death. Since the uncovering of the underlying genetic defect in cystic fibrosis (CF), our knowledge of the disease process has increased substantially, but we still lack a holistic approach to its management, which comprises of multiple facades, requiring both pharmacological and non-pharmacological or rehabilitatory approaches. So far, the therapeutic options were limited to targeting the consequences and complications of the disease, such as respiratory infection, mucus retention, pancreatic insufficiency, etc., but now several promising therapies may be able to address the underlying pathology rather than its long-term effects. This review summarizes the current and upcoming pharmacological options for CF, such as those targeting the CFTR gene defect directly, including gene editing, CFTR correctors and potentiators; drugs targeting the epithelial sodium channels (ENaC inhibitors); repositioning of some existing drugs and evaluating their role in CF; and understanding the disease better by transcriptomic approaches and the role of gut microbiota in the disease process and severity.