From target discovery to clinical drug development with human genetics

K Trajanoska, C Bhérer, D Taliun, S Zhou, JB Richards… - Nature, 2023 - nature.com
The substantial investments in human genetics and genomics made over the past three
decades were anticipated to result in many innovative therapies. Here we investigate the …

The future of cystic fibrosis care: a global perspective

SC Bell, MA Mall, H Gutierrez, M Macek… - The Lancet …, 2020 - thelancet.com
Executive summary The past six decades have seen remarkable improvements in health
outcomes for people with cystic fibrosis, which was once a fatal disease of infants and young …

Pharmacologic improvement of CFTR function rapidly decreases sputum pathogen density, but lung infections generally persist

DP Nichols, SJ Morgan, M Skalland… - The Journal of …, 2023 - Am Soc Clin Investig
Background Lung infections are among the most consequential manifestations of cystic
fibrosis (CF) and are associated with reduced lung function and shortened survival. Drugs …

Clinical effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: a clinical trial

DP Nichols, AC Paynter, SL Heltshe… - American journal of …, 2022 - atsjournals.org
Rationale: The cystic fibrosis (CF) modulator drug, elexacaftor/tezacaftor/ivacaftor (ETI),
proved highly effective in controlled clinical trials for individuals with at least one F508del …

Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double …

HGM Heijerman, EF McKone, DG Downey… - The Lancet, 2019 - thelancet.com
Background Cystic fibrosis transmembrane conductance regulator (CFTR) modulators
correct the basic defect caused by CFTR mutations. Improvements in health outcomes have …

[HTML][HTML] Triple Therapy for Cystic Fibrosis Phe508del–Gating and –Residual Function Genotypes

PJ Barry, MA Mall, A Álvarez, C Colombo… - … England Journal of …, 2021 - Mass Medical Soc
Background Elexacaftor–tezacaftor–ivacaftor is a small-molecule cystic fibrosis
transmembrane conductance regulator (CFTR) modulator regimen shown to be efficacious …

Physiology and pathophysiology of human airway mucus

DB Hill, B Button, M Rubinstein… - Physiological …, 2022 - journals.physiology.org
The mucus clearance system is the dominant mechanical host defense system of the human
lung. Mucus is cleared from the lung by cilia and airflow, including both two-phase gas-liquid …

CFTR modulators: the changing face of cystic fibrosis in the era of precision medicine

M Lopes-Pacheco - Frontiers in pharmacology, 2020 - frontiersin.org
Cystic fibrosis (CF) is a lethal inherited disease caused by mutations in the CF
transmembrane conductance regulator (CFTR) gene, which result in impairment of CFTR …

Future therapies for cystic fibrosis

L Allen, L Allen, SB Carr, G Davies, D Downey… - Nature …, 2023 - nature.com
We are currently witnessing transformative change for people with cystic fibrosis with the
introduction of small molecule, mutation-specific drugs capable of restoring function of the …

A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele

ET Zemanick, JL Taylor-Cousar, J Davies… - American journal of …, 2021 - atsjournals.org
Rationale: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and
safe in patients≥ 12 years of age with cystic fibrosis and at least one F508del-CFTR (cystic …