Molecular basis of cystic fibrosis and modern therapeutic approaches

Identifikacija molekularne povezanosti između genske nefunkcionalnosti CFTR gena te patofiziološke i kliničke pozadine cistične fibroze omogućila je razvoj suvremenih terapijskih modela koji su primarno utemeljeni na individualiziranom pristupu oboljelima. Klasifikacija velikog spektra mutacijskih promjena postala je izuzetno važna komponenta u personaliziranoj medicini koja pokušava pristupiti svakom pojedinom pacijentu na specifičan način koji će omogućiti najefikasnije djelovanje molekularnih agensa usmjerenih na povrat izgubljene stanične funkcije mutiranih stanica primarno respiratornog sustava koji je temljeni uzrok visoke smrtnosti oboljelih osoba. Evolucijski značaj cistične fibroze te njezina velika populacijska zastupljenost potakla je značajan interes znanstvene zajednice u identifikaciji terapijskih strategija koje se ne temelje na liječenju simptoma već na genskoj terapiji i uređivanju genoma, modulatorskim molekulama koje pokušavaju povratiti pravilan unutarstanični transport i proteinsku funkciju CFTR-a te konačno zamjenskim ionskim kanalima koji uspostavljaju alternativne prijenosne puteve. Navedeni pristupi danas nailaze na mnoge zapreke u smislu dizajna, uspješnosti prijenosa i djelotvornosti kao i financijske održivosti, ali njihova visoka specifičnost i mogućnost značajnog smanjenja smrtnosti potiče njihov daljnji razvoj i budući napredak u klinici, komercijalnoj dostupnosti i primjenjivosti unutar područja personalizirane medicine.Identification of molecular association between genetic dysfunction of the CFTR gene and pathophysiological and clinical background of cystic fibrosis has enabled the development of modern therapeutic approaches that are becoming predominantly personalised. The precise classification of the whole spectrum of mutations has become an extremely important component in CF personalised medicine that attempts to approach each individual in a specific way that will allow the choice of the most efficient molecular agents. These agents are aimed at regaining the lost cellular function of mutated cells, primarily of respiratory system which represents the main cause of high mortality among people suffering from cystic fibrosis. Evolutionary significance of cystic fibrosis and its large prevalence in the population have led to a great interest of scientific community in identifying therapeutic strategies that are not based on treatments aimed at reducing symptoms but rather on gene therapy, genome editing and application of modulator molecules. Along modulators, which attempt to restore normal intracellular transport and consequently protein function, replacement ion channels are also becoming an important therapeutic asset in activation of alternative transport pathways aiming to restore native cellular function. Nowadays, these approaches face many obstacles in aspects of drug design, transfer efficiency and effectiveness as well as financial sustainability but their high specificity and ability to significally reduce mortality enables their further development and future progresses in clinical, commercial availability and applicability within personalized medicin