UF Researchers: Gene Therapy Method To Treat Cystic Fibrosis Is Safe

Published: October 25 1996

Category:Health, Research

ORLANDO—An experimental method of delivering gene therapy into the damaged airways of cystic fibrosis patients is safe, University of Florida researchers announced today (10/25) at the 10th Annual North American Cystic Fibrosis Conference.

Scientists also said the approach successfully transferred normal copies of the gene that is defective in cystic fibrosis patients into cells lining the respiratory tract, but cautioned further studies are needed to determine whether the procedure successfully combats the most prevalent lethal hereditary disease in America.

The strategy was the first to use a new molecular “vehicle” known as the adeno-associated virus, or AAV, which already enjoys a harmonious and symptomless existence in many humans. Scientists equipped the virus with an important “passenger,” the healthy gene.

“Our study has shown successful transfer of DNA in the nose in a majority of patients, with no evidence of toxicity,” said Dr. Terence Flotte, a pediatrician, geneticist and microbiologist with UF’s College of Medicine. “That much we know and can say with confidence.”

Physicians delivered the gene through a thin plastic tube into one side of the nose and through a fiber-optic bronchoscope into the lower right lobe of the lung. UF participants were treated in the federally funded Clinical Research Center at Shands at UF. Researchers at UF and Johns Hopkins have treated nine cystic fibrosis patients since the study began in November, 1995.

Scientists determined whether the gene was transferred successfully by brushing cells from the lining of the nose and lung to see if they incorporated correct copies of the gene.

Previous studies have used adenovirus as a carrier. But despite its similar-sounding name, it actually differs greatly from AAV. Some studies have shown adenovirus causes inflammation of the respiratory tract, leading to a pneumonia-like syndrome in many cystic fibrosis patients.

“The key to any therapy is being able to get the desired effect at a dose that is free of side effects. This is an improvement over adenovirus, which has caused inflammation at a dose very close to the dose needed to see any positive effects,” said Flotte, who also co-directs UF’s Gene Therapy Center. “Our study of AAV has shown that we can safely administer this viral carrier to a larger number of patients during a later trial.”

Study participants will continue to be followed for a one-year period from the time of their entry into the trial.

Flotte and Barrie Carter, executive vice president and director of research and development at Seattle-based Targeted Genetics Corp., are credited with identifying the so-called AAV “vector” and developing the technology for its use while at the National Institutes of Health in the early 1990s.

Flotte continued researching the vector at Johns Hopkins, and transferred the program when he joined UF earlier this month. The five-year program is funded by NIH and the Cystic Fibrosis Foundation.

Cystic fibrosis, the so-called “thief of breath,” robs patients of life by slowly destroying their lungs through recurrent infections. An estimated 30,000 Americans have it. The disease stems from a faulty gene that causes the normal passage of salt and water through the body’s cells to go haywire. Among the most severe consequences is a build-up of excessive amounts of thick mucus in the lower airways of the lungs — often leading to permanent lung damage. Most patients die before they reach 30.

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Melanie Fridl Ross

Category:Health, Research