GAINESVILLE---Using an increasingly promising tool from their gene therapy arsenal, scientists have hit on an innovative way to replace a crucial protein that protects the lungs from the destructive action of an often-fatal lung-liver disease, University of Florida researchers report in the Proceedings of the National Academy of Science.
The approach employs a virus modified to incorporate the protein missing in people with alpha-1-antitrypsin deficiency, which causes early emphysema and severe liver disease. UF scientists injected the virus, known as the adeno-associated virus, into muscle tissue in mice, checking to see whether the protein would be secreted into the bloodstream.
Not only did the method work, but for the first time researchers were able to generate levels of the protein high enough to be therapeutic in humans - a major step ahead. Furthermore, the results were sustained for more than four months with a single injection.
Previous attempts at gene therapy have been hampered by scientists' inability to attain protein levels in the bloodstream high enough to be beneficial and for as long as needed.
"The thing about alpha-1 that makes it a potentially difficult target for gene therapy is that very high serum levels are required to prevent the development of emphysema," said Dr. Terry Flotte, an associate professor of pediatrics, molecular genetics and microbiology and co-director of the Gene Therapy Center at UF's College of Medicine. "The big advance in what we did was that we were able to achieve a circulating level in the blood that would be therapeutic in humans.
"It's quite promising for therapy -- it's essentially all we needed for proof of the concept."
Considered the second most-common genetic disorder among Caucasians, A1AD
affects an estimated 100,000 Americans. One in 50 carries the gene for it.
Alpha-1-antitrypsin is produced by the liver and protects the lungs from
injury by a common enzyme that normally f
Contact: Melanie Fridl Ross
University of Florida