Cystic fibrosis: current therapeutic targets and future approaches

Abstract

ObjectivesStudy of currently approved drugs and exploration of future clinical development pipeline therapeutics for cystic fibrosis, and possible limitations in their use.MethodsExtensive literature search using individual and a combination of key words related to cystic fibrosis therapeutics.Key findingsCystic fibrosis is an autosomal recessive disorder due to mutations in CFTR gene leading to abnormality of chloride channels in mucus and sweat producing cells. Respiratory system and GIT are primarily involved but eventually multiple organs are affected leading to life threatening complications. Management requires drug therapy, extensive physiotherapy and nutritional support. Previously, the focus was on symptomatic improvement and complication prevention but recently the protein rectifiers are being studied which are claimed to correct underlying structural and functional abnormalities. Some improvement is observed by the corrector drugs. Other promising approaches are gene therapy, targeting of cellular interactomes, and newer drugs for symptomatic improvement.ConclusionsThe treatment has a long way to go as most of the existing therapeutics is for older children. Other limiting factors include mutation class, genetic profile, drug interactions, adverse effects, and cost. Novel approaches like gene transfer/gene editing, disease modeling and search for alternative targets are warranted.

Failure to Thrive: Bad Nutrition as a Double-Edged Sword - A Case Report

“…It comprises multiple respiratory and gastrointestinal complications like bronchiectasis and chronic infections that eventually lead to respiratory failure [5]. Concerning respiratory tract infections and respiratory symptoms, these were all denied by the mother and there are no records of Emergency Room (ER) visits that could confirm this fact.…”

“…Other complications like hepatic dysfunction, gallstones and intestinal obstruction may also develop in CF patients [5].…”

CFTR activity is enhanced by the novel corrector GLPG2222, given with and without ivacaftor in two randomized trials

“…Approximately 90% of people with cystic fibrosis (CF) have at least one copy of the F508del mutation and around half of these individuals are F508del homozygous [5]. Current treatment approaches aimed at CF transmembrane conductance regulator (CFTR) modulation in F508del homozygous subjects have their limitations.…”

Should isolated Pseudo‐Bartter syndrome be considered a CFTR‐related disorder of infancy?

“…There are more than 70 000 CF patients worldwide and approximately 1000 new cases are diagnosed every year, with the highest incidence in people of Northern European ancestry . Currently, CF diagnosis is made by positive newborn screening (NBS), or presentation of typical symptoms and a chloride sweat test >60mmol/L and/or genetic analysis of CFTR gene identifying two CF causing mutations …”