Cystic FIbrosis Flashcards
CF affects how many people in the U.S. and in the world respectively?
30,000
70,000
What does CF ultimately cause?
Sticky unusually thick mucus
What happens when CF mucus is produced?
It clogs lungs
Causes lung infections
Obstructs pancreas
Affects enzymes from food break down and food absorption
How many new cases of CF are diagnosed each year?
1,000 per year
Life expectancy of CF patients?
30s 40s and beyond
What gene is defective in CF patients?
CFTR (CF transmembrane conductance regulator) gene
What is the best way to diagnose cystic fibrosis?
Sweat test
How to interpret the sweat test?
High NaCl levels indicate CF
When was the CFTR gene discovered?
1989
What is the specific gene defect in CTFR gene?
F508del
What does the majority of morbidity and mortality come from in CF?
Pulmonary disease associated with chronic bronchial infections
What is the most common bacterial infection in CF?
Pseudomonas aeruginosa
What do all CF disease causing mutations result in?
Defective cAMP-regulated Cl- secretion by epithelial cells
What is a Class I mutation of CFTR?
Impaired protein production (premature termination codons)
What is a Class II mutation of CFTR?
Affect CFTR protein processing due to misfolding (mutation in F508del and others)
What is a Class III mutation of CFTR?
Disruption in channel regulation through impaired gating (G551D)
What is a Class IV mutation of CFTR?
Decrease Cl- ion conductance through the Cl- channel
What is a class V mutation of CFTR?
Significant reduction of normal protein levels
What is a class VI mutation of CFTR?
Decreased retention/anchoring at the cell surface
What does the Cl- concentration have to be in order for a patient to have CF?
Greater than 60 mM/L
How many CFTR mutations are disease causing?
177
Class I treatment:
Aminoglycoside antibiotics
Class II treatment:
Chemical and molecular chaperones can potentially promote protein folding
Class III treatment:
CFTR channel activators (VX-770 ivacaftor)
Class IV treatment:
Compensation for reduced conductance
Class V treatment:
Antisense oligonucleotides
Class VI treatment:
Compounds that enhance CFTR anchoring on cell surface
What channel is being studied to rectify defective Cl- channels?
Ca2+ activated Cl- channels
What are ENaC?
Epithelial sodium channels
What do ENaC channels do?
Intake Na from the lumen
What is the significance of ENaC?
They are needed to pump Na into the lumen drawing water with it and making the mucus less thick
What activates purinergic receptors?
ATP
UTP
Denusofol
What do activated purinergic receptors do?
Inhibits ENaC
Activates CaCC
What do CaCC channels do?
Pumps Cl- into the lumen
What is another name for CaCC?
AN01 (sought after to be activated)
What is the first drug to treat underlying cause of CF in a small group of people with CF?
Kalydeco aka Ivacaftor
In patients with two copies of F508del mutation what is the current treatment?
Ivacaftor in combination with lumacaftor
In patients with two copies of F508del what drug improves lung function and weight gain?
Orkambi
What is ivacaftor?
CFTR activator
What is lumacaftor?
Protein folding chaperone
What is Orkambi?
Combination of ivacaftor and lumacaftor
