Personalized Medicine; a Potential Therapy for Cystic Fibrosis
Abstract
Cystic Fibrosis (CF) is an inherited disorder caused by mutations in CFTR gene that codes for Cystic Fibrosis Transmembrane-conductance Receptor anion channel. It is an autosomal recessive disease which affects the cells that secrete sweat, mucous and digestive juice, making these fluids thick and sticky, thus plugging ducts and tubes of various organs. The CF mutations are classified into various classes (class I, II, III, IV, V and VI) based on the cellular phenotype and complexity of mutants. The knowledge and understanding of biology and mechanisms of defects that underlie Cystic fibrosis paved a way to the development of different therapeutic approaches for these mutation classes. Ivacaftor first CFTR potentiator (FDA approved in 2012) is mostly used for Class III and IV mutations. Trials in patients with homozygous F508del mutation, a most common type of CF mutation that involves protein processing defects, showed no improvement with Ivacaftor alone, therefore, a double-combination therapy involving potentiator-corrector i.e., Ivacaftor-Lumacaftor got approval in 2015 to treat patients homozygous for F508del mutation. Then Ivacaftor-Tezacaftor (corrector) combination therapy was approved in 2018 which showed improved tolerability as compared to lumacaftor. In 2019, Trikfta, a triple combination therapy, came into light. It increases CFTR activity and is substantially considered to work more effectively in patients homozygous for F508del mutation. Studies and clinical trials reveal the outperformance of Trikafta in other available therapies in terms of respiratory symptoms, lungs functionality and quality of life on a whole.
Keywords: Cystic Fibrosis (CF); Cystic Fibrosis Transmembrane Conductance regulator (CFTR); Ivacaftor; Lumacaftor; Tezacaftor; Trikafta
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DOI: http://dx.doi.org/10.62940/als.v9i4.1510
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