The PROMPTLY study is a proof-of-concept research project evaluating the efficacy of XHALIP, an innovative inhalable formulation of Imatinib, in treating pulmonary arterial hypertension (PAH) and post-inflammatory fibrosing lung diseases (LFD). Main Objective To demonstrate the ability of XHALIP to improve the prognosis of PAH and LFD by reducing pulmonary fibrosis and vascular remodeling. Key Research Questions Is XHALIP effectively absorbed by pathological lung cells? Does it have a beneficial biological effect on cell proliferation and extracellular matrix deposition? Study Plan Preclinical phase: In vitro tests on cells obtained from patients with PAH and LFD. Absorption and distribution analysis: In vitro lung tissue models to assess drug penetration and effectiveness. Biological activity assessment: Evaluating XHALIP's ability to inhibit epithelial-mesenchymal transition and cell proliferation. Participants Patients aged ≥ 18 years diagnosed with PAH or LFD, either candidates for or recipients of lung transplantation. Biological samples (bronchoalveolar lavage and explanted lung tissues). Methodology Confocal microscopy and flow cytometry to analyze absorption. RT-PCR and Western Blot to assess biological efficacy. Alveolo-capillary models to test drug release and distribution. The study aims to translate preclinical findings into a potential future clinical trial for the development of XHALIP as a novel inhalation-based therapeutic strategy for rare lung diseases.
Study Type
OBSERVATIONAL
Enrollment
16
Fondazione IRCCS Policlinico San Matteo
Pavia, Pavia, Italy
RECRUITINGComplete synthesis and characterization of XHALIP for in vitro studies.
Preparation and stabilization of the dry powder formulation of XHALIP.
Time frame: two years from the enrollment
Complete synthesis and characterization of XHALIP for in vitro studies.
Evaluation of XHALIP uptake by various cell types obtained ex vivo from patients with LFD and PAH, as well as transplant recipients (endothelial, epithelial, MC, PASMC, inflammatory effector cells), cultured in vitro and in co-culture systems.
Time frame: two years from the enrollment
Complete synthesis and characterization of XHALIP for in vitro studies.
Evaluation of CD44 expression by various cell types obtained ex vivo from patients with LFD and PAH, as well as transplant recipients (endothelial, epithelial, MC, PASMC, inflammatory effector cells), cultured in vitro and in co-culture systems.
Time frame: two years from the enrollment
Exploration of XHALIP Distribution
The distribution of XHALIP will be studied in thin lung tissue cultures (Precision Cut Lung Slices Cells, PCLSC) obtained from lung explants of patients with LFD and PAH.
Time frame: two years from the enrollment
Exploration of XHALIP Distribution
XHALIP distribution will be explored in a model that replicates the alveolo-capillary microenvironment to analyze its interaction with specific pathological human cells and mucosal/surfactant layers, as well as its ability to cross the alveolo-capillary interface.
Time frame: two years from the enrollment
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