Drug combination therapies to treat the underlying cause of Cystic Fibrosis are a promising strategy and here is why: Cystic Fibrosis is a result of specific mutations that occurs in the CFTR gene, resulting in a defect CFTR protein. The combination therapies currently being tested are targeting 2 crucial steps in the maturation and function of the CFTR protein (see below figure).
A “corrector” drug rescues a mis-folded protein (step 1) and brings it to the cell membrane. Then, a “potentiator” drug rescues the protein function (step 2) and keeps the channel open, allowing more chloride ions (green) out of the cells and onto the lung surface (which in turn attracts water and hydrates the lungs).
The leading drug from Vertex Pharmaceuticals, Kalydeco (ivacaftor) is a "potentiator" drug and rescues protein function in step 2. However, the most common mutation that causes CF (Del F508) affects the folding of the protein (step 1), hence Kalydeco has no effect.
The new drug(s) being tested in combination with Kalydeco try to rescue to protein folding (step 1). They are thus "corrector drugs". This will allow combination therapies to be useful for people with Del F508 mutations (60-70% of CFers).
View attachment 455
Please feel free to post any questions below or contribute to the discussion currently taking place on our facebook page:
https://www.facebook.com/knowcf/pho...385540.257971313776/10152905208703777/?type=1
- Chris Baldwin, PhD
CEO at CysticFibrosis.com
Friend me! https://www.facebook.com/cysticfibrosisdotcom
A “corrector” drug rescues a mis-folded protein (step 1) and brings it to the cell membrane. Then, a “potentiator” drug rescues the protein function (step 2) and keeps the channel open, allowing more chloride ions (green) out of the cells and onto the lung surface (which in turn attracts water and hydrates the lungs).
The leading drug from Vertex Pharmaceuticals, Kalydeco (ivacaftor) is a "potentiator" drug and rescues protein function in step 2. However, the most common mutation that causes CF (Del F508) affects the folding of the protein (step 1), hence Kalydeco has no effect.
The new drug(s) being tested in combination with Kalydeco try to rescue to protein folding (step 1). They are thus "corrector drugs". This will allow combination therapies to be useful for people with Del F508 mutations (60-70% of CFers).
View attachment 455
Please feel free to post any questions below or contribute to the discussion currently taking place on our facebook page:
https://www.facebook.com/knowcf/pho...385540.257971313776/10152905208703777/?type=1
- Chris Baldwin, PhD
CEO at CysticFibrosis.com
Friend me! https://www.facebook.com/cysticfibrosisdotcom