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Cystic Fibrosis is an autosomal recessive disorder with no cure. It is one of the most common life-shortening genetic diseases in the Caucasian population, affecting more than 75000 individuals worldwide. This inherited multi-organ disease is associated with chronic lung infection, malabsorption, salt loss syndrome, infertility and numerous other comorbidities. Understanding the cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation and function of CFTR protein has offered personalized treatment strategies to help those with CF. From in-vitro and in-vivo studies to pre-clinical and clinical trials, therapeutic drugs are finally having an impact, yet there are many more specific treatments under clinical investigation. This article summarizes the ongoing advances and technology in understanding the treatment of CF from more than two decades.