Systems Pharmacology of Cystic Fibrosis Transmembrane Regulator Correctors and Potentiators

Grant number: 1157287 | Funding period: 2019 - 2023

Completed

Abstract

Cystic fibrosis is a life limiting disease caused by defective or deficient cystic fibrosis trans-membrane conductance regulator activity. The recent approval of lumacaftor combined with ivacaftor targets 70% of CF patients with F508del-CFTR. Unfortunately, the clinical efficacy of these first-in-class drugs is limited by our limited understanding of their pharmacology. This innovative systems pharmacology project will have a significant potential in improving clinical practice worldwide.

Related publications (23)

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A Perspective on the Role of Metformin in Treating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID

D Fineberg, A Moreau, EK Schneider-Futschik, CW Armstrong

2025-10-10

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID (LC) are increasingly recognized as debilitating postin..

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Hyperfiltration and Elevated Fractional Excretion of Magnesium in Children with Cystic Fibrosis

EK Schneider-Futschik, CB Munro, D Li, S Ranganathan, C Quinlan

2025-09-12

Several critical knowledge gaps exist in understanding and managing renal function in pediatric patients with cystic fibrosis (CF)..

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Investigating the Potential Hearing Impairment and Ototoxicity in Children up to Six Years With Cystic Fibrosis After Aminoglycoside Exposure (PIANO-CF Extension)

EK Schneider-Futschik, CB Munro, C Quinlan, S Ranganathan

2025-02-01

Background: People with CF (pwCF) are often treated with prolonged courses of aminoglycosides (AGs), for which known adverse effec..

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Predictive capacity of paediatric nasal epithelial cells in sequential CFTR modulator therapy

LK Fawcett, ZA Chew, EK Schneider-Futschik, KM Allan, HR Patel, A Jaffe, S Waters

2025-01-01

Background CFTR modulators have transformed cystic fibrosis (CF) treatment, but individual responses vary even among patients with..

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The role of CFTR in the eye, and the effect of early highly effective modulator treatment for cystic fibrosis on eye health

EK Schneider-Futschik, Y Zhu, D Li, MD Habgood, BN Nguyen, I Pankonien, MD Amaral, LE Downie, HR Chinnery

2024-11-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is a protein that plays a crucial role in various human organs, includi..

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Extent of foetal exposure to maternal elexacaftor/tezacaftor/ivacaftor during pregnancy

D Li, M Donnelley, D Parsons, MD Habgood, EK Schneider-Futschik

2024-08-01

Background and Purpose: Cystic fibrosis (CF) patients are living longer and healthier due to improved treatments, e.g. cystic fibr..

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Recommended Tool Compounds for Modifying the Cystic Fibrosis Transmembrane Conductance Regulator Channel Variants

XX Han, D Li, Y Zhu, EK Schneider-Futschik

2024-04-12

Cystic fibrosis (CF) is a genetic disorder arising from variations in the cystic fibrosis transmembrane conductance regulator (CFT..

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Fetal drug exposure after maternally administered CFTR modulators Elexacaftor/Tezacaftor/Ivacaftor in a rat model

D Li, Y Zhu, M Donnelley, D Parsons, MD Habgood, EK Schneider-Futschik

2024-02-01

Background: The potential effects of the very effective cystic fibrosis triple combination drug, Elexacaftor/Tezacaftor/Ivacaftor ..

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Dry Powder Inhalation for Lung Delivery in Cystic Fibrosis

X Han, D Li, F Reyes-Ortega, EK Schneider-Futschik

2023-05-01

Pulmonary drug delivery has long been used for local and systemic administration of different medications used in acute and chroni..

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In Utero Mapping and Development Role of CFTR in Lung and Gastrointestinal Tract of Cystic Fibrosis Patients

D Li, XX Han, M Habgood, EK Schneider-Futschik

2023-03-10

In cystic fibrosis (CF) the ability of the CF transmembrane conductance regulator (CFTR) protein to mediate chloride and water tra..

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Current and Emerging Inhaled Antibiotics for Chronic Pulmonary Pseudomonas aeruginosa and Staphylococcus aureus Infections in Cystic Fibrosis

D Li, EK Schneider-Futschik

2023-03-01

Characterized by impaired mucus transport and subsequent enhanced colonization of bacteria, pulmonary infection causes major morbi..

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Gastrointestinal consequences of lipopolysaccharide-induced lung inflammation

RM McQuade, M Bandara, S Diwakarla, L Sahakian, MN Han, M Al Thaalibi, MR Di Natale, M Tan, KH Harwood, EK Schneider-Futschik, A Jarnicki

2023-01-01

Background: Respiratory inflammation is the body’s response to lung infection, trauma or hypersensitivity and is often accompanied..

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Ocular development after highly effective modulator treatment early in life

Y Zhu, D Li, F Reyes-Ortega, HR Chinnery, EK Schneider-Futschik

2023-01-01

Highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies (HEMT), including elexacaftor..

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Editorial: Women in pharmacology of infectious diseases: 2021

EK Schneider-Futschik, I Spriet, H Zhou

2022-10-06

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Chronic Lung and Respiratory Conditions Affecting Lungs and Airways

EK Schneider-Futschik

2022-09-09

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Ivacaftor Alters Macrophage and Lymphocyte Infiltration in the Lungs Following Lipopolysaccharide Exposure

KH Harwood, RM McQuade, A Jarnicki, EK Schneider-Futschik

2022-06-10

Background and purpose: Cystic fibrosis (CF) is associated with a myriad of respiratory complications including increased suscepti..

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Editorial: Functional Characterization and Pharmaceutical Targets in Common and Rare CFTR Dysfunctions

EK Schneider-Futschik, VH Lobert, JW Wilson

2022-01-24

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Entry of cystic fibrosis transmembrane conductance potentiator ivacaftor into the developing brain and lung

F Qiu, MD Habgood, Y Huang, KM Dziegielewska, S Toll, EK Schneider-Futschik

2021-09-01

Background: The potential effects of ivacaftor during pregnancy and breastfeeding on the offspring are still unknown. This study a..

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Insights Into Patient Variability During Ivacaftor-Lumacaftor Therapy in Cystic Fibrosis

PO Hanafin, I Sermet-Gaudelus, M Griese, M Kappler, H Ellemunter, C Schwarz, J Wilson, M Tan, T Velkov, GG Rao, EK Schneider-Futschik

2021-08-02

Background: The advent of cystic fibrosis transmembrane conductance regulator protein (CFTR) modulators like ivacaftor have revolu..

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Advantages and disadvantages of using magnetic nanoparticles for the treatment of complicated ocular disorders

EK Schneider-Futschik, F Reyes-Ortega

2021-08-01

Nanomaterials provide enormous opportunities to overcome the limitations of conventional ocular delivery systems, such as low ther..

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Anti-inflammatory influences of cystic fibrosis transmembrane conductance regulator drugs on lung inflammation in cystic fibrosis

KH Harwood, RM McQuade, A Jarnicki, EK Schneider-Futschik

2021-07-02

Cystic fibrosis (CF) is caused by a defect in the cystic fibrosis transmembrane conductance regulator protein (CFTR) which instiga..

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Successes and challenges: Inhaled treatment approaches using magnetic nanoparticles in cystic fibrosis

M Tan, F Reyes-Ortega, EK Schneider-Futschik

2020-06-01

Magnetic nanoparticles have been largely applied to increase the efficacy of antibiotics due to passive accumulation provided by e..

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Emerging Cystic Fibrosis Transmembrane Conductance Regulator Modulators as New Drugs for Cystic Fibrosis: A Portrait of in Vitro Pharmacology and Clinical Translation

DP Ghelani, EK Schneider-Futschik

2020-02-14

Pharmacological correction of the defective ion channel with cystic fibrosis transmembrane conductance regulator (CFTR) has become..

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