The care of CF patients who possess mutations responsive to available CFTR modulators has changed dramatically in recent years. If new modulators being tested in the clinic perform as hoped, the majority of patients with CF could be treated with at least one drug targeted to the underlying cause of their disease. However, a subset of rare variants will not share the benefit of these developments. In particular, patients with premature stop codons, splice defects, conductance mutations, and refractory folding mutants, such as N1303K, will remain an unmet need. To expand novel treatments to all patients, a deeper understanding of these variants is needed. In this session, we will explore current knowledge of these challenging molecular pathologies.
Discuss the molecular and functional phenotypes of rare disease-causing variants (including premature stop codons, splicing mutations, and conductance mutations) and outline potential therapeutic strategies for correcting them in cystic fibrosis.
Describe development of new tools to understand the molecular and functional features of rare mutations, including those that could enable screening to identify novel therapeutics.
Define why challenging folding mutants, such as N1303K, are refractory to currently approved CFTR modulators.
Note: Speaker Batsheva Kerem's presentation was not recorded at her request.