Notes+on+cystic+fibrosis+investigational+therapies+2-4-13

Notes on cystic fibrosis investigational therapies 2-4-13

q The survival rate of patients with cystic fibrosis (CF) continues to improve.

q In 1985, the median predicted survival was 25 years of age, while in 2008 it had increased to 37 years

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q Class II mutations: Defective protein processing — Mutations causing defective protein processing are the most common cause of CF worldwide

q The incorrectly folded protein is then recognized by the cell as defective ^ I wonder how the cell recognizes this

q High-throughput screening of large combinatorial chemical libraries identified candidate molecules (called “correctors”) that allow F508del CFTR to be transported to the apical surface. One such drug, VX-809

q High-throughput screening of combinatorial libraries has identified candidate molecules (called “potentiators”) that improve activation of these abnormal channels and enhance chloride flux in cells expressing at least some of these class III mutations.

q Ivacaftor (VX-770, Vertex pharmaceuticals) is a potentiator drug that has substantial benefits ^for some patients

q Activating alternative chloride channels — Airway epithelial cells possess chloride channels other than CFTR, such as the calcium-activated chloride channel, and activation of such channels might compensate for the loss of CFTR activity.

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