Treatment for Cystic Fibrosis Flashcards
(13 cards)
Managing lung problems
physical therapy
- exercise and medication
- to decrease mucus blockade of airways
chest therapy
- bronchial or postural drainage
- vibrate chest to dislodge mucus
exercise
- helps loosen mucus
- stimulates coughing to clear mucus
medications
- bronchodilators
- mucolytics
- decongestants
- antibiotics - fight infections
surgery
- heart and lung transplant
- disease does come back
Managing digestive problems
- more easily managed than lung problems
- well-balanced, high caloric diet (low fat, high protein
- pancreatic enzyme therapy
- vitamin supplements
- enemas and mucolytic enzymes
- liver transplant
Class I mutations and treatment
- caused by early stop codons
- severe phenotype - no CFTR
- aminoglycosides to suppress premature stop codons e.g. gentamycin
Class II mutations and treatment options
- severe phenotype - defective CFTR processing and trafficking
- no cell surface chloride ion transport
- if misfolded triangleF508 gets to the membrane, it can work, but only 25% gets there!
- deletion of F508 = disturbance of CFTR interactions with chaperones and ER
- premature removal and proteolysis
- phenylbutyrate = increased eNaC expression
- circumin in tumeric may help?
- sildenafil = increased chloride secretion in CF tissue
- salmeterol = increased forskolin-mediated chloride efflux in triangleF508 CFTR-expressing cells
- lumacaftor-stimulated chloride activity
Class III mutations and treatment
- severe phenotype - defective chloride channel regulation
- decreased chloride ion transport
- resistant to phosphorylation or ATP binding
- ivacaftor = CFTR potentiator; orally bioavailable; increased time CFTR remains open - augments chloride transport activity of G55ID-CFTR
Class IV and V mutations
- mild phenotype
- class IV = reduced chloride conductance
- class V = reduced number of normal CFTR proteins
Gene therapy - retroviruses
ssRNA converted to DNA for integration into host cell genome
+ integrate genes into host DNA
+ long-term stability
- random integration
- disruption of host genes
- only infect dividing cells
Gene therapy - adenoviruses
no need for integration into host DNA
+ don’t cause disease
+ large capacity
- transient expression
- attacked by immune system
Gene therapy - liposomes
+ no viral genes
+ don’t cause disease
- less efficient
- soapy
Gene therapy - naked DNA
+ no viral genes
+ don’t cause disease
- less efficient
- unstable in most tissues
Types of gene therapy
- retrovirus
- adenovirus
- liposomes
- naked DNA
Transport to the apical membrane
How to get vectors through?
- delivered from basolateral membrane to access receptors
- transiently disrupt tight junctions using calcium chelation or hypotonic solutions
- modify membrane so binds vectors
- engineer vectors to bear ligands which bind apical surface e.g. GPCRs
Cholera toxin as a treatment
- treatment for CF?
- could dilute mucus
- cholera toxin strengthens airway mucosa immunity
- slows airway remodelling
