School of Health Sciences


Biology: Cell and Molecular Biology


CF, CFTR, Modulator, Cystic Fibrosis, Trikafta, Ivacaftor, Lumacaftor, Tezacaftor, Elexacaftor


Chemical and Pharmacologic Phenomena | Chemicals and Drugs | Circulatory and Respiratory Physiology | Medical Pharmacology | Respiratory Tract Diseases


Developing a drug therapy that addresses the root cause of cystic fibrosis (CF) by increasing CFTR protein levels has long been a research challenge. After genetic therapy failed because a suitable delivery system could not be found, researchers began searching for small organic molecules that could act as chaperones for CFTR. These molecules, known as modulators, allowed CFTR to be assembled correctly and function similarly to wild type CFTR. Since 2012, four modulator drugs have been developed, tested, and approved by the FDA. In October 2019, Trikafta was approved as the first triple-combination modulator drug and has completely revolutionized CF therapy. This paper details the research challenges, successes, and failures that led to the development of modulator therapies.