Cystic fibrosis (CF) is an autosomal recessive disease in which mutations in the CFTR gene cause various symptoms through its channel malfunction. Among over 1900 gene mutations, the most common mutation is ΔF508 which causes a trafficking defect of CFTR to plasma membrane (classified as ‘class II’ ). CF is quite rare in Japanese and listed in ‘Intractable Diseases’ by MHLW, Japan.
The most frequent point-mutations in Japanese patients are H1085R and L441P, both are class II same as ΔF508. Recently the FDA granted Vertex Inc. approval for "Trikafta", a combination of two expression correctors, elexacaftor and tezacaftor, and one channel function potentiator, ivacaftor. In Japan, at present, the CF treatment is limited to some symptomatic ones, and no radical treatment has not been approved yet. Trikafta could be effective against disease-associated mutations other than ΔF508.
In this presentation, we will discuss about the therapeutic effects of Tricafta against H1085R and L441P, based on our in vitro data.