L29- Modulators Flashcards
What kind of nonspecific treatments are there
Pert, antistaph/anti pseudomonas’s, physiotherapy, mycolytics, dnases
What was the first modulator found and for whcih mutation
Ivacaftor for class 3 eg gly551asp (problems with gating)
What does it do
Augments Cl transport, asl volume increase, cilia beat frequency increase and sweat cl reduction
Which article discusses ivacaftors effect more
Ramsey et Al 2011
By how much was sweat Cl reduced in 48 weeks
48.1 mmol/L
What was the exacerbation reduction rate
55%
How much did fev1 increase by
10.6%
What weight gain was there
2.8kg
What did brodlie et al 2015 find about ivacaftor
Works for other type 3 mutations like arg117his
Does not work for phe508 mutation
Ivacaftor is a potentiator what is this
Increase the open probability of CFTR channel ie better gating
What are correctors
Modulators which increase processing and trafficking of the CFTR eg for class 2 mutations
When Ivacaftor was tested for the phe508 what happened (brodlie 2015)
No change in fev, sweat Cl or weight
What was the first corrector-potentiator treatment and which article talks about it
Lumacaftor-ivacaftor
Wainwright et al 2015
What was the fev1 improvement
4% which was still much less than Ivacaftor for the g551d
What other changes were there in early clinical trials
BMI , exacerbation rate and sweat Cl
What was the issue with it
Was no cost benefit to it and 4.2% reported side effects like dyspnoea and liver problems
What was the next corrector looked at
Tezacaftor
What does it do (brodlie 2015)
Helps correct folding and processing to the surface
What sort of effects did it have (brodlie 2015)
Reduced sweat Cl and better fev sligjtly and less side effects than lumicaftor
What was found in people with heterozygous mutation for phe508
Tezacaftor didn’t work, no sig change to fev
Which therapy was first for heterozygous phe508 patients
Triple therapy (elexacaftor-Tezacaftor-Ivacaftor)
Which article talks more about this triple therapy
Middleton 2019
What % reduction in exacerbations were there
63% (even more than Ivacaftor)
What did the fev increase by even more than Ivacaftor
14.3% change
What we’re the side effects like
Very mild only 1% discontinued
Why is there no drugs for class 5 and 6
Too rare to find patients for the clinical trials
Which other mutation has issues in finding treatments
Class 1
