Circulating Biomarkers From the Phase 1 Trial of Sirolimus and Autophagy Inhibition for Patients With Lymphangioleiomyomatosis

Chest
Anthony M LamattinaSouheil El-Chemaly

Abstract

We have previously conducted the Sirolimus and Autophagy Inhibition in LAM (SAIL) trial, a phase 1 dose-escalation study of the combination of sirolimus and hydroxychloroquine in patients with lymphangioleiomyomatosis (LAM). The goal of the present study was to analyze sera from the SAIL trial to identify novel biomarkers that could shed light into disease pathogenesis and response to therapy. We used the DiscoveryMAP platform from Rules Based Medicine to simultaneously measure 279 analytes in sera collected at each visit from subjects enrolled in the SAIL trial. We used longitudinal regression and pathway analysis to examine analyte rate of change and corresponding effect on lung function and to identify networks and potential nodes of interest. A total of 222 analytes were included in the analysis. We identified 32 analytes that changed over the treatment period of the study. Pathway analysis revealed enrichment in cytokine-receptor interaction and mechanistic/mammalian target of rapamycin-related pathways, in addition to seemingly unrelated processes such as rheumatoid arthritis. Search Tool for the Retrieval of Interacting Genes/Proteins analysis identified two hubs centered around acetyl-CoA carboxylase alpha and beta and ...Continue Reading

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Citations

Nov 6, 2018·The European Respiratory Journal·Heng-Jia Liu, Elizabeth P Henske
Mar 30, 2019·Orphanet Journal of Rare Diseases·Anthony M LamattinaSouheil El-Chemaly
May 16, 2020·Frontiers in Pharmacology·Ferda KaleağasıoğluMartin R Berger
Oct 23, 2019·Cancers·Marta Pérez-HernándezVanessa Soto-Cerrato
Mar 7, 2021·International Journal of Molecular Sciences·Jilly Frances EvansVera P Krymskaya

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