Development of individual therapy for cystic fibrosis using primary epithelial tissue cultures

Development of individual therapy for cystic fibrosis using primary epithelial tissue cultures - Precision study

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON43765

Enrollment

Registered

2016-11-16

Start date

2017-02-14

Completion date

Unknown

Last updated

2024-08-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

cystic fibrosis

Interventions

None listed

Eligibility

Age

2 Years to 17 Years

Inclusion criteria

Inclusion criteria: - Signed Informed Consent - 0-18 years of age - Two CF-causing CFTR mutations (or not known, in case of the control population) - Undergoing a bronchoscopy for diagnostic purposes

Exclusion criteria

Exclusion criteria: - CF related liver disease with abnormal coagulation

Design outcomes

Primary

Measure	Time frame
The correlation between CFTR genotype, CFTR residual function and response to currently available therapy assessed in epithelial cells of bronchial, nasal or rectal origin in vitro, and how these parameters associate with individual in vivo clinical disease measures (FEV1, sweat chloride concentration, BMI, infection, etc).	—

Secondary

Measure	Time frame
Scientific proof of concept studies to identify potential variables for individual CF disease development and treatment efficacy: - Characterization of CFTR DNA sequence variability (using TLA sequencing), mRNA (qRT-PCR) and protein expression (Western blotting and immunofluorescence) between patients samples. - Characterization of epithelial barrier functions in response to pathogen challenge (CFTR function, mucus production, cilia function, cytokine production, cell differentiation and viability, pathogen killing) and upon pharmacological and genetic interventions - Functional and genetic characterization of genetic modifiers of CF disease (e.g. alternative channel, transcription factors) using DNA sequencing (whole genome sequencing will be done for CF tissues, potential modifiers will be validated using the control population), pharmacological treatments and genetic engineering of cells - identification of CFTR-dependent cellular biomarkers (mRNA, protein, and metabolome profiling) using pharmacological treatments and genetic engineering of cells Feasibility studies aiming to setup novel airway cultures and CFTR-dependent readouts. - ability to generate and maintain airway organoid cultures and use for study of CFTR function and CF modifiers - ability to generate and maintain submucosal gland cells in culture and use for study of CFTR function and CF modifiers.	—

Measure

Time frame

Scientific proof of concept studies to identify potential variables for individual CF disease development and treatment efficacy: - Characterization of CFTR DNA sequence variability (using TLA sequencing), mRNA (qRT-PCR) and protein expression (Western blotting and immunofluorescence) between patients samples. - Characterization of epithelial barrier functions in response to pathogen challenge (CFTR function, mucus production, cilia function, cytokine production, cell differentiation and viability, pathogen killing) and upon pharmacological and genetic interventions - Functional and genetic characterization of genetic modifiers of CF disease (e.g. alternative channel, transcription factors) using DNA sequencing (whole genome sequencing will be done for CF tissues, potential modifiers will be validated using the control population), pharmacological treatments and genetic engineering of cells - identification of CFTR-dependent cellular biomarkers (mRNA, protein, and metabolome profiling) using pharmacological treatments and genetic engineering of cells Feasibility studies aiming to setup novel airway cultures and CFTR-dependent readouts. - ability to generate and maintain airway organoid cultures and use for study of CFTR function and CF modifiers - ability to generate and maintain submucosal gland cells in culture and use for study of CFTR function and CF modifiers.

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Countries

Netherlands

Outcome results