Lecture 5

Question 1

what are the 2 different bands of CFTR?

Answer 1

lower molecular weight = immature, not fully glycosylated,

higher molecular weight = fully glycosylated CFTR that goes into the membrane and functions

Question 2

Impact of lumacaftor on deltaF508 mutations?

Answer 2

total amount of mature CFTR increases – bypass immature version being sent for degradation
increased short circuit current
increased Cl secretion and better CFTR function

Question 3

why could lumacaftor and ivacaftor be used in combination therapy?

Answer 3

• Lumacaftor = Corrector – drives CFTR to the surface - push mutant channel to membrane
• Ivacaftor = Potentiator – helps open the channels - increase open probability

Question 4

what does a forrest plot show?

Answer 4

Range of parameters youre interested in

Look at whether placebo patients have a better profile than the treatment patients

Question 5

features of Tezacaftor & ivacaftor together?

Answer 5

Tezacaftor = corrector – drives CFTR to the surface
Ivacaftor = potentiator – increases open probability
heterozygous - small increase in mature CFTR, no signif increase in chloride transport
homozygous - significant increase - poss significant increase in chloride transport

Question 6

features of Elexacaftor, tezacaftor & ivacaftor

Answer 6

biggest increase In cftr in homozygous cells

All 3 – 4/5 fold increase in chloride transport – seen in both sets of cells

Question 7

why would you use amiloride?

Answer 7

gets rid of ENaC