Researchers develop novel gene/cell therapy approach for lung disease

PUBLIC RELEASE DATE:

1-Oct-2014

Contact: Nick Miller nicholas.miller@cchmc.org 513-803-6035 Cincinnati Children's Hospital Medical Center @CincyChildrens

CINCINNATI Researchers developed a new type of cell transplantation to treat mice mimicking a rare lung disease that one day could be used to treat this and other human lung diseases caused by dysfunctional immune cells.

Scientists at Cincinnati Children's Hospital Medical Center report their findings in a study posted online Oct. 1 by Nature. In the study, the authors used macrophages, a type of immune cell that helps collect and remove used molecules and cell debris from the body.

They transplanted either normal or gene-corrected macrophages into the respiratory tracts of mice, which were bred to mimic the hereditary form of a human disease called hereditary pulmonary alveolar proteinosis (hPAP). Treatment with both normal and gene-corrected macrophages corrected the disease in the mice.

"These are significant findings with potential implications beyond the treatment of a rare lung disease," said Bruce Trapnell, MD, senior author and a physician in the Division of Neonatology and Pulmonary Biology at Cincinnati Children's. "Our findings support the concept of pulmonary macrophage transplantation (PMT) as the first specific therapy for children with hPAP"

"Results also identified mechanisms regulating the numbers and phenotype of macrophages in the tiny air sacs of the lungs (called alveoli) in health and disease," said Takuji Suzuki, MD, PhD, the study's first author and a scientist in the Division of Neonatology and Pulmonary Biology at Cincinnati Children's.

Suzuki and Trapnell discovered hPAP at Cincinnati Children's and first reported it in 2008. In hPAP, the air sacs become filled with surfactant, a substance the lungs produce to reduce surface tension and keep the air sacs open. 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 of these children.

The used surfactant builds up in the lungs, filling the alveoli and causing difficult breathing or respiratory failure. The only current treatment for these children is whole-lung lavage, an invasive lung-washing procedure performed under general anesthesia. Although the procedure works, it is temporary, must be repeated frequently, and creates quality of life issues for affected children.

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Researchers develop novel gene/cell therapy approach for lung disease