Role of Extracellular Vesicles as Biomarkers of Pulmonary Involvement in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex

Condition(s) studied

Investigational drug(s) / intervention(s)

Pulmonary Function Test: Spirometry, Plethysmography, Diffusing capacity of the lungs for carbon monoxide (DLCO), and Six-minute walk test (6MWT).

Analysis of Extracellular Vesicles: From the venous blood sample, plasma will be separated, and extracellular vesicles (EVs) will be isolated through serial centrifugation steps. The EVs will be analyzed to assess their concentration (particles/mL) and size (nanometers, nm). Additionally, omics analyses will be performed to study the molecular content of the EVs, including nucleic acids, proteins, and lipids.

Study summary

Lymphangioleiomyomatosis (LAM) is a rare lung disease, linked to Tuberous Sclerosis Complex (TSC) or occurring sporadically, and involves abnormal mTORC1 activation. LAM cells are neoplastic, and recent focus has turned to extracellular vesicles (EVs), which mediate tumor progression and may serve as biomarkers. This study, conducted at the Pulmonology Unit of ASST Santi Paolo e Carlo and the Pharmacology Laboratory of the University of Milan, will analyze the characteristics of serum EVs in patients with LAM and TSC. During scheduled outpatient visits, clinical and functional data and blood samples will be collected. Plasma will be separated, and EVs will be isolated via centrifugation. EVs will be analyzed for size, concentration, and molecular content (proteins, lipids, nucleic acids). The results obtained will be collected and correlated with the clinical and functional data.

Eligibility

Primary outcome measure(s)

• To compare the number and morphological characteristics of Extracellular Vesicles (EVs) in women with S-LAM, TSC-LAM, TSC without pulmonary involvement, and healthy controls — One year
  The concentration (particles/mL) and the size (nm) of EVs isolated from the plasma of 3 groups of patients (sporadic LAM, LAM associated to TSC, TSC without pulmonary involvement) and of 1 healthy control group will be assessed through Nanoparticle Tracking Analysis.

Trial sites (1)

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