A toxicology study of Csf2ra complementation and pulmonary macrophage transplantation therapy of hereditary PAP in mice.

ABSTRACT: Pulmonary macrophage transplantation (PMT) is a gene and cell transplantation approach in development as therapy for hereditary pulmonary alveolar proteinosis (hPAP), a surfactant accumulation disorder caused by mutations in CSF2RA/B (and murine homologs). We conducted a toxicology study of PMT of Csf2ra gene-corrected macrophages (mGM-Rα⁺Mϕs) or saline-control intervention in Csf2ra^KO or wild-type (WT) mice including single ascending dose and repeat ascending dose studies evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics. Lentiviral-mediated Csf2ra cDNA transfer restored GM-CSF signaling in mGM-Rα⁺Mϕs. Following PMT, mGM-Rα⁺Mϕs engrafted, remained within the lungs, and did not undergo uncontrolle

SUBMITTER: Arumugam P 

PROVIDER: S-EPMC11001781 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature