Disrupting Six/Eya Signalling as New Therapy for Lung Fibrosis

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is the most common type of interstitial lung disease, with a median survival of 2-4 years from the time of diagnosis [1]. It is estimated that the prevalence of IPF in the US is approximately 10-60 cases per 100,000 people, with limited pharmacological therapies available [2, 3]. IPF is a chronic, progressive disease characterized by alveolar injury, increased extracellular matrix (ECM) deposition and resultant alveolar destruction. Macroscopically, this leads to poor lung compliance, impaired trans-alveolocapillary membrane gas exchange and ultimately, end-stage respiratory failure, necessitating lung transplantation [2, 4, 5]. Several non-genetic risk factors, such as male sex, older age, and smoking, increase the risk of developing IPF [4, 6]. More recently, several genetic risk factors for IPF have also been discovered, including a single-nucleotide polymorphism (rs35705950) in the promoter region of MUC5B [7-9], which codes for an essential protein for airway clearance and innate immune response, along with genes associated with telomere maintenance, such as telomerase RNA component (TERC) and telomerase reverse transcriptase (TERT) [1, 10].