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Researchers discover gene therapy to prevent progression of emphysema
Date:12/21/2009

(Boston) Researchers from Boston University School of Medicine (BUSM) have discovered a new gene therapy that may prevent the progression of emphysema. The study, which appears on-line in the Journal of Clinical Investigation, describes a method to express therapeutic genes in lung tissue for a lifetime after only a single treatment.

Alpha-1 Anti-trypsin Deficiency is the most common inherited form of emphysema seen in young people due to a mutation in the Alpha-1 Anti-trypsin gene. This genetic disease predisposes affected individuals to early emphysema and cirrhosis of the liver.

According to the researchers, gene transfer into specific cell lineages in vivo remains an attractive yet elusive approach for correcting inherited mutations. Although a variety of techniques have been developed to deliver DNA molecules to cells in vitro, in vivo gene transfer has been limited in many cell types by inefficient gene delivery as well as the limited life-span of differentiated cell types

Using mice, the BUSM researchers discovered a system to deliver genes selectively to as many as 70 percent of a mouse lung's alveolar macrophages (AM), a key cell type contributing to emphysema.

"We applied this novel approach to achieve sustained in vivo expression of normal human alpha-1 antitrypsin (hAAT) protein at levels able to ameliorate emphysema in mice," said senior author Darrell Kotton, MD, an associate professor of medicine and pathology and co-director, Center for Regenerative Medicine at BUSM. "The lung macrophages carrying the therapeutic gene survived in the lungs air sacks for the two-year lifetime of the treated mice following a single intra-tracheal injection of the lentiviral vector we had engineered," he added.

Kotton and his colleagues utilized this method of gene transfer to achieve localized secretion of therapeutic levels of human alpha-1 antitrypsin (hAAT) protein in lung epithelial lining fluid. "The prog
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Contact: Gina M. DiGravio
gina.digravio@bmc.org
617-638-8480
Boston University Medical Center
Source:Eurekalert

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