Next Article in Journal
Neuron-Radial Glial Cell Communication via BMP/Id1 Signaling Is Key to Long-Term Maintenance of the Regenerative Capacity of the Adult Zebrafish Telencephalon
Next Article in Special Issue
CFTR Protein: Not Just a Chloride Channel?
Previous Article in Journal
Neurons Are a Primary Driver of Inflammation via Release of HMGB1
Previous Article in Special Issue
Anti-Inflammatory and Anti-Oxidant Effect of Dimethyl Fumarate in Cystic Fibrosis Bronchial Epithelial Cells
 
 
Review

Therapeutic Approaches for Patients with Cystic Fibrosis Not Eligible for Current CFTR Modulators

by 1,2,* and 2,3,4
1
AP-HP. Centre—Université de Paris, Hôpital Cochin, Centre de Référence Maladie Rare-Mucoviscidose, 75014 Paris, France
2
Faculté de Médecine, Université de Paris, 75006 Paris, France
3
INSERM U 1151, Institut Necker Enfants Malades, 75015 Paris, France
4
AP-HP. Centre—Université de Paris, Hôpital Necker Enfants Malades, Centre de Référence Maladie Rare-Mucoviscidose, 75015 Paris, France
*
Author to whom correspondence should be addressed.
Academic Editor: Massimo Conese
Cells 2021, 10(10), 2793; https://doi.org/10.3390/cells10102793
Received: 23 September 2021 / Revised: 11 October 2021 / Accepted: 15 October 2021 / Published: 19 October 2021
(This article belongs to the Collection Cystic Fibrosis: Cells, Physiopathology and Emerging Therapies)
Cystic fibrosis is a severe autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding the CFTR protein, a chloride channel expressed in many epithelial cells. New drugs called CFTR modulators aim at restoring the CFTR protein function, and they will benefit many patients with cystic fibrosis in the near future. However, some patients bear rare mutations that are not yet eligible for CFTR modulators, although they might be amenable to these new disease-modifying drugs. Moreover, more than 10% of CFTR mutations do not produce any CFTR protein for CFTR modulators to act upon. The purpose of this review is to provide an overview of different approaches pursued to treat patients bearing mutations ineligible for CFTR modulators. One approach is to broaden the numbers of mutations eligible for CFTR modulators. This requires developing strategies to evaluate drugs in populations bearing very rare genotypes. Other approaches aiming at correcting the CFTR defect develop new mutation-specific or mutation-agnostic therapies for mutations that do not produce a CFTR protein: readthrough agents for nonsense mutations, nucleic acid-based therapies, RNA- or DNA-based, and cell-based therapies. Most of these approaches are in pre-clinical development or, for some of them, early clinical phases. Many hurdles and challenges will have to be solved before they can be safely translated to patients. View Full-Text
Keywords: cystic fibrosis; CFTR modulators; readthrough agents; RNA therapy; gene therapy; gene editing; cell-based therapy cystic fibrosis; CFTR modulators; readthrough agents; RNA therapy; gene therapy; gene editing; cell-based therapy
Show Figures

Figure 1

MDPI and ACS Style

Fajac, I.; Sermet, I. Therapeutic Approaches for Patients with Cystic Fibrosis Not Eligible for Current CFTR Modulators. Cells 2021, 10, 2793. https://doi.org/10.3390/cells10102793

AMA Style

Fajac I, Sermet I. Therapeutic Approaches for Patients with Cystic Fibrosis Not Eligible for Current CFTR Modulators. Cells. 2021; 10(10):2793. https://doi.org/10.3390/cells10102793

Chicago/Turabian Style

Fajac, Isabelle, and Isabelle Sermet. 2021. "Therapeutic Approaches for Patients with Cystic Fibrosis Not Eligible for Current CFTR Modulators" Cells 10, no. 10: 2793. https://doi.org/10.3390/cells10102793

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop