Cystic Fibrosis

Question 1

what is personalised medicine?

Answer 1

a branch of medicine using the patient’s information i.e. gene, proteins and environment, to prevent, diagnose an treat the disease.

Question 2

what is pharmacogenomics?

Answer 2

-focusing on identifying genome variants which influence drug effects (pharmacokinetics and pharmacodynamics)

Question 3

what does a lower blood eosinophil count correlate with?

Answer 3

a greater risk f developing pneumonia

Question 4

what is the function of the respiratory tract?

Answer 4

gas exchange and host defence

Question 5

explain what the mucociliary clearance does?

Answer 5

cilia movement sweeps mucous out of the lungs and towards the mouth

Question 6

what is the role of the CFTR protein?

Answer 6

-to maintain the flow of ions (Na+ and Cl-) and water in and out of the cells

Question 7

what does CFTR stand for?

Answer 7

cystic fibrosis transmembrane conductance regulator

Question 8

what results when the CFTR protein doesn’t work anymore in cystic fibrosis?

Answer 8

• there becomes an unequal salt balance, hence mucus production becomes thick and sticky disabling cilia movement.
• resulting in a build up (thickening) of the sticky mucus hence narrowing the airways.

Question 9

what organs are affected by cystic fibrosis?

Answer 9

1. sweat glands
2. liver
3. pancreas
4. digestive tract

Question 10

what are the 6 classes of cystic fibrosis mutations?

Answer 10

1. lack of CFTR synthesis (no transcription)
2. defective protein processing (CFTR made is immature so isn’t modified in smooth ER)
3. defective channel regulation/gating (doesn’t work like it should)
   4) defective chloride conductance
   class
   5) reduced CFTR protein as defect in splicing
   6) Increased turnover of CFTR channel at cell surface (doesn’t stay at the cell surface membrane)

Question 11

what genotype specific small molecule drugs are used to modulate CFTR function?

Answer 11

1. potentiators
2. correctors
3. production correctors/read-through agents

Question 12

what do potentiators do?

Answer 12

-increase CFTR function when it’s expressed at the apical surface of epithelial cells. This corrects class 3 and 4 CFTR mutations.

Question 13

what do correctors do?

Answer 13

-improve the intracellular processing and delivery of mutant CFTR protein in class 2 mutations so more proteins reach the cell surface.

Question 14

what do production correctors/read through agents do?

Answer 14

-promote the read-through of Premature Terminating Codons (PTCs) in mRNA allowing CFTR protein production in class 1 mutations.

Question 15

what class are most CFTR mutations associated with?

Answer 15

class 2 and 3

Question 16

what class mutation does ataluren target?

Answer 16

class 1

Question 17

what class mutation does ivacaftor target?

Answer 17

class 3 and 4

Question 18

what class mutation does lumacaftor target?

Answer 18

class 2

Question 19

what is the combination therapy given to treat CFTR?

Answer 19

lumacaftor for class 2 and ivacaftor for class 3 mutation treatments. They’re given together

Question 20

how does a loss of CFTR function result in ductal obstruction?

Answer 20

loss of CFTR function inhibits secretion of digestive enzymes and bicarbonates into the duodenum-they remain in the pancreatic duct. This causes an obstruction in the duct as enzymes accumulate. This can cause long-term problems