Macrophage transplantation could become therapy for hPAP
A new type of cell transplantation may one day become a treatment for hereditary pulmonary alveolar proteinosis (hPAP) and certain other rare lung diseases.
Bruce Trapnell, MD, and Takuji Suzuki, MD, PhD, discovered hPAP at Cincinnati Children’s and first reported it in 2008. Children with hPAP have mutations in the genes of GM-CSF receptor alpha or beta (CSFR2RA or CSFR2RB). These mutations reduce the ability of alveolar macrophages to remove used surfactant from the lungs, which can lead to respiratory failure. The only current treatment is repeated, invasive whole-lung lavage.
In a recent study published in Nature, Suzuki and Trapnell report that macrophage transplantation (involving normal or gene-corrected cells) fully reversed the disease in mice bred to mimic hPAP. The treatment also prevented disease-specific mortality for at least one year.
“These are significant findings with potential implications beyond the treatment of a rare lung disease,” said Trapnell, senior author, and a researcher in the Translational Pulmonary Science Center at Cincinnati Children’s. “Our findings support the feasibility of pulmonary macrophage transplantation as the first specific therapy for children with hPAP.”
The research team utilized mice with the homologous Csf2rb gene knocked out that mimic hPAP. The team then used a viral vector to deliver a correct version of Csf2rb to abnormal alveolar macrophages taken from the animals. The gene-corrected cells were returned to the mice by direct instillation into the lungs.
Since publication, the researchers have begun the pre-clinical studies needed to prepare for human clinical trials.
