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Splicing mutation
- Question
- Hello
Are they any studies underway for splicing mutations?
If yes, what are they?
Thank you for your answer. - Answer
- Hello,
A lot of studies are underway to study splicing CFTR mutations. The impact of these mutations varies according to their localisation, classifying them as “severe” or “mild” mutations. Patients carrying such mutations could have a classic or a moderate form of the disease accordingly to the splicing mutation itself and the second mutation they carry. Biologist and geneticist teams study these mutations at the molecular level to define their effect on the CFTR protein.
To more specifically focus the novel therapies that have recently emerged in cystic fibrosis, some target the defective CFTR protein itself. As such, they differ according to the CFTR mutation classes. Actually, six classes are generally distinguished: 1) I : absence of protein ; 2) II : defect of the cellular maturation of the protein; 3) III : non-functional protein ; 4) IV : dysfunction of the protein ; 5) V : less protein : 6) VI : stability of the protein altered. The 3 first classes are classified as “severe” and the other as “mild” mutations.
Severity of splicing mutations differs accordingly to their effect on the protein itself: they could be classified as severe (class I) or mild (class V). In the class I mutations, some are associated to premature stop codons. For these, a new treatment is under evaluation: Ataluren® (PTC124). The first trials that have been conducted so far have had encouraging results, reporting improvement in chloride transport in adults and children with cystic fibrosis. Efficacy on other clinical parameters are underway like lung function, pulmonary exacerbations and quality of life. It is actually unknown whether this new molecule could target splicing mutations.
For all the CF patients, independently to their mutations, a lot of studies are underway to improve the disease symptoms. For example, for respiratory symptoms, therapies are tested to improve airway clearance or to reduce respiratory inflammation. These trials could of course concern patients with splicing mutations (link for drug trials in CF: www.cff.org/research/DrugDevelopmentPipeline). I hope to have answered your question. Regards,
Harriet Corvol - 05.05.2011
