CFTR functional assays in drug development

Abstract

ABSTRACTIntroduction: Cystic Fibrosis (CF) is the most common fatal genetic disease in persons of Northern European ancestry. It is an autosomal recessive disease caused by loss of function of the cystic fibrosis transmembrane conductance regulator protein (CFTR), a transmembrane chloride and bicarbonate channel. Traditional management of CF targets symptoms, while recently developed therapies (modulators) directly improve CFTR function.Areas covered: This article highlights in vitro methods that have broadened the understanding of CFTR structure and function and led to the development of CFTR modulators, in vivo methods to clinically assess CFTR function and modulation, and ex vivo methods that directly evaluate CFTR activity in specific cell types. Focus will be placed on how these assays bring new drugs from initial discovery to patient use.Expert opinion: Use of currently available CFTR assays from the lab to the patient and back will empower a robust program of drug discovery and expansion across CF patients with both common and rare CFTR mutations. This capacity exists, but requires optimization and integration to be fully realized. The ability to measure drug bioactivity at the protein level across numerous systems represents an unprecedented opportunity to further care of patients with CF.