Innovative Therapy and Underlaying Mechanism of Neuraminidase-1-Driven Pulmonary Fibrosis

Abstract

Tissue fibrosis contributes to multiple diseases within every organ and tissue. Better therapies need to be developed. We recently identified an enzyme, neuraminidase (NEU) 1, as a key player in fibrosis. Specific Aim 1 to preclinically develop a novel, NEU1-targeting, antifibrotic therapy. In the first year of funding, we performed experiments to comparatively assess various routes of drug delivery based on evaluation of sustained inhibition of NEU1. The results indicate that parenteral (injected) route provides the most efficient as well as prolonged inhibition of NEU1 compared with the oral route. This is an important finding that will support further development of the drug towards transition to human trials beyond the scope of this project. In addition to this work, we identified a protein called MUC1 as a NEU1 substrate and demonstrated that desialylation enhances its downstream signaling. Specific Aim 2 to explore whether MUC1 mediates the profibrotic effect of NEU1 will be pursued in the second year of this project.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2022
Accession Number
AD1161290

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  • Irina G. Luzina

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