Translational Research in Cystic Fibrosis: From Bench to Beside

Overview

Journal Front Pediatr

Specialty Pediatrics

Date 2022 Jun 2

PMID 35652053

Authors

Laura de Castro E Garcia

Lucas Montiel Petry

Pedro Augusto Van Der Sand Germani

Luiza Fernandes Xavier

Paula Barros de Barros

Amanda da Silva Meneses

Laura Menestrino Prestes

Luana Braga Bittencourt

Marina Puerari Pieta

Frederico Friedrich

Leonardo Araujo Pinto

Affiliations

Soon will be listed here.

Abstract

Cystic fibrosis is the most common life-limiting recessive genetic disorder in Caucasian populations, characterized by the involvement of exocrine glands, causing multisystemic comorbidities. Since the first descriptions of pancreatic and pulmonary involvement in children, technological development and basic science research have allowed great advances in the diagnosis and treatment of cystic fibrosis. The great search for treatments that acted at the genetic level, despite not having found a cure for this disease, culminated in the creation of CFTR modulators, highly effective medications for certain groups of patients. However, there are still many obstacles behind the treatment of the disease to be discussed, given the wide variety of mutations and phenotypes involved and the difficulty of access that permeate these new therapies around the world.

Citing Articles

Immunohistochemical detection of MUC5AC and MUC5B mucins in ferrets.

Meyerholz D, Leidinger M, Adam Goeken J, Businga T, Vizuett S, Akers A BMC Res Notes. 2023; 16(1):111.

PMID: 37349833 PMC: 10286488. DOI: 10.1186/s13104-023-06388-x.

Changes of Erythrocyte Fatty Acids after Supplementation with Highly Concentrated Docosahexaenoic Acid (DHA) in Pediatric Cystic Fibrosis: A Randomized Double-Blind Controlled Trial.

Ayats-Vidal R, Bosque-Garcia M, Cordobilla B, Asensio-De la Cruz O, Garcia-Gonzalez M, Castro-Marrero J J Clin Med. 2023; 12(11).

PMID: 37297899 PMC: 10253750. DOI: 10.3390/jcm12113704.

Editorial: Translational research in pediatric respiratory diseases: From bench to bedside.

Hijano D, Alvarez-Paggi D, Caballero M Front Pediatr. 2023; 10:1114549.

PMID: 36683809 PMC: 9853422. DOI: 10.3389/fped.2022.1114549.

References

di SantAgnese P, DARLING R, PERERA G, Shea E . Abnormal electrolyte composition of sweat in cystic fibrosis of the pancreas; clinical significance and relationship to the disease. Pediatrics. 1953; 12(5):549-63. View

Ratjen F, Hug C, Marigowda G, Tian S, Huang X, Stanojevic S . Efficacy and safety of lumacaftor and ivacaftor in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2017; 5(7):557-567. DOI: 10.1016/S2213-2600(17)30215-1. View

Misbahuddin M Rafeeq , Murad H . Cystic fibrosis: current therapeutic targets and future approaches. J Transl Med. 2017; 15(1):84. PMC: 5408469. DOI: 10.1186/s12967-017-1193-9. View

Taylor-Cousar J, Munck A, McKone E, van der Ent C, Moeller A, Simard C . Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med. 2017; 377(21):2013-2023. DOI: 10.1056/NEJMoa1709846. View

Bell S, Mall M, Gutierrez H, Macek M, Madge S, Davies J . The future of cystic fibrosis care: a global perspective. Lancet Respir Med. 2019; 8(1):65-124. PMC: 8862661. DOI: 10.1016/S2213-2600(19)30337-6. View

Navarro S . [Historical compilation of cystic fibrosis]. Gastroenterol Hepatol. 2015; 39(1):36-42. DOI: 10.1016/j.gastrohep.2015.04.012. View

Rommens J, Iannuzzi M, Kerem B, Drumm M, Melmer G, Dean M . Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989; 245(4922):1059-65. DOI: 10.1126/science.2772657. View

Merkert S, Schubert M, Olmer R, Engels L, Radetzki S, Veltman M . High-Throughput Screening for Modulators of CFTR Activity Based on Genetically Engineered Cystic Fibrosis Disease-Specific iPSCs. Stem Cell Reports. 2019; 12(6):1389-1403. PMC: 6565754. DOI: 10.1016/j.stemcr.2019.04.014. View

Shteinberg M, Haq I, Polineni D, Davies J . Cystic fibrosis. Lancet. 2021; 397(10290):2195-2211. DOI: 10.1016/S0140-6736(20)32542-3. View

10.

De Wilde G, Gees M, Musch S, Verdonck K, Jans M, Wesse A . Identification of GLPG/ABBV-2737, a Novel Class of Corrector, Which Exerts Functional Synergy With Other CFTR Modulators. Front Pharmacol. 2019; 10:514. PMC: 6521598. DOI: 10.3389/fphar.2019.00514. View

11.

Middleton P, Mall M, Drevinek P, Lands L, McKone E, Polineni D . Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019; 381(19):1809-1819. PMC: 7282384. DOI: 10.1056/NEJMoa1908639. View

12.

Kerem B, Rommens J, Buchanan J, Markiewicz D, Cox T, Chakravarti A . Identification of the cystic fibrosis gene: genetic analysis. Science. 1989; 245(4922):1073-80. DOI: 10.1126/science.2570460. View

13.

Riordan J, Rommens J, Kerem B, Alon N, Rozmahel R, Grzelczak Z . Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989; 245(4922):1066-73. DOI: 10.1126/science.2475911. View

14.

Ramos K, Pilewski J, Taylor-Cousar J . Challenges in the use of highly effective modulator treatment for cystic fibrosis. J Cyst Fibros. 2021; 20(3):381-387. PMC: 8192344. DOI: 10.1016/j.jcf.2021.01.007. View

15.

Berg A, Hallowell S, Tibbetts M, Beasley C, Brown-Phillips T, Healy A . High-Throughput Surface Liquid Absorption and Secretion Assays to Identify F508del CFTR Correctors Using Patient Primary Airway Epithelial Cultures. SLAS Discov. 2019; 24(7):724-737. DOI: 10.1177/2472555219849375. View

16.

Keating D, Marigowda G, Burr L, Daines C, Mall M, McKone E . VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018; 379(17):1612-1620. PMC: 6289290. DOI: 10.1056/NEJMoa1807120. View

17.

Wainwright C, Elborn J, Ramsey B, Marigowda G, Huang X, Cipolli M . Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N Engl J Med. 2015; 373(3):220-31. PMC: 4764353. DOI: 10.1056/NEJMoa1409547. View

18.

Jensen T, Loo M, Pind S, Williams D, GOLDBERG A, Riordan J . Multiple proteolytic systems, including the proteasome, contribute to CFTR processing. Cell. 1995; 83(1):129-35. DOI: 10.1016/0092-8674(95)90241-4. View

19.

Sturm R . An advanced stochastic model for mucociliary particle clearance in cystic fibrosis lungs. J Thorac Dis. 2012; 4(1):48-57. PMC: 3256542. DOI: 10.3978/j.issn.2072-1439.2011.09.09. View

20.

Veit G, Avramescu R, Chiang A, Houck S, Cai Z, Peters K . From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations. Mol Biol Cell. 2016; 27(3):424-33. PMC: 4751594. DOI: 10.1091/mbc.E14-04-0935. View