leky-latky/cftr-protein/mutace/mutace-1

Aminoglycoside antibiotics

• Can suppress premature termination codons by disrupting translational fidelity
• Allowing the incorporation of an amino acid
• Thus permitting translation to continue to the normal termination of the transcript [8]

Ataluren

• Allows the read through of premature stop codons, and studies in patients with CF with nonsense mutations show an increase in chloride transportation.
• Ataluren requires 3 times a day dosing and is currently in a Phase 3 placebo-controlled study. [10]

Topická aplikace gentamycinu

• A recent double-blind, placebo-controlled, crossover study
• Restoration of CFTR function by topical application of gentamicin to the nasal epithelium of cystic fibrosis patients carrying stop mutations
• 21% of the patients - complete normalization of all the electrophysiologic abnormalities caused by the CFTR defect
• 68% there was restoration of either chloride or sodium transport
• Immunohistochemical staining to the C-terminal part of the CFTR
• Peripheral staining for CFTR in scraped nasal epithelial cells [9]

• Achieving CFTR activity of 10 to 35%
• Might be needed to prevent significant pulmonary morbidity. [9]

I.v. podání gentamycinu

• Suppression of stop mutations in the CFTR gene with parenteral gentamicin can be predicted in vitro and is associated with clinical benefit and significant modification of the CFTR-mediated Cl- transport in nasal and sweat gland epithelium.

Class I mutations

• Nonsense mutations
• Result in the presence of a premature stop codon
• Production of unstable mRNA / release from the ribosome of a short, truncated protein that is not functional
• 5 to 10% of the total mutant alleles in cystic fibrosis patients
• Certain subpopulations the incidence is much higher [9]