Inhaled GM-CSF Therapy of Autoimmune Pulmonary Alveolar Proteinosis

National Center For Advancing Translational Sciences

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Linked publications & trials

Abstract

Pulmonary alveolar proteinosis (PAP) is a rare disease marked by accumulation of proteins and lipids in the narrow gas exchange pockets of the lung, leading to respiratory failure. PAP is an autoimmune disorder in which patients generate antibodies against a normal protein found in the circulation (GM-CSF), which is a critical modulator of macrophage development. When circulating macrophages are impaired, they are unable to reach the lungs and clear the accumulated proteins and lipids. The goal of this project is to develop inhaled GM-CSF as therapy for PAP. As GM-CSF is currently used as an intravenous treatment for other conditions, the Food and Drug Administration has required the completion of a formal toxicology study to ensure safety before proceeding to further clinical trials in humans for PAP. A comprehensive project plan was developed by TRND and the lead collaborators at Cincinnati Childrens Hospital Medical Center. The team subsequently entered into collaboration with Genzyme Corporation, now Sanofi Genzyme, who are providing essential research materials to the partnership. TRND scientists supported extensive preliminary primate toxicology and dosing studies necessary to demonstrate the safety of using inhaled GM-CSF. TRND also supported formal Good Laboratory Practice (GLP) toxicology studies that enabled the lead collaborator to receive clearance from the FDA to initiate clinical trials. TRND is supporting a Phase 1 pharmacokinetic and pharmacodynamic study in PAP patients.