Eric Sorscher and colleagues at UAB developed two different ways to overcome the genetic mutations responsible for cystic fibrosis.
Cystic fibrosis is a hereditary disease caused by mutations in a single gene, the cystic fibrosis transmembrane conductance regulator (CFTR). Since the gene was first identified in 1989, scientists have been searching for a way to correct the defect. UAB researchers have found two. Now they are working to perfect these techniques and bring them to bear against a devastating airway disorder.
UAB scientists at the Gregory Fleming James Cystic Fibrosis Research Center, led by Eric Sorscher, M.D., were pioneers in efforts to replace the CFTR gene with a properly working copy. Sorscher’s team was the first in the United States to successfully introduce the corrected gene to the nasal passages of a human patient in 1995 and then directly to the lung in 1997.
These trials showed that the concept worked, but there were obstacles to overcome, primarily in coping with inflammation and achieving the necessary number of copies of the gene in the airways. Teams from UAB and around the world are working to surmount these issues by improving the existing delivery method. They are also developing a viral delivery system that may help them achieve enough efficiency to make treatments viable.
Another approach, driven in large measure by discoveries at UAB that ferreted out CFTR’s secrets over the years, takes a new angle. Instead of replacing the broken gene, this strategy works to repair it. Clinical studies led by David Bedwell, Ph.D., JP Clancy, M.D., and Steve Rowe, M.D., are investigating small molecule drugs to overcome different mutations in CFTR. Due to the reputation of its team of basic scientists and clinicians, UAB’s CF Center has taken the lead in three international research consortiums that are developing these small molecules—and established itself as a global leader in cystic fibrosis research and treatment.
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