Gainesville Man Is Florida’s First Cystic Fibrosis Patient To Receive Gene Therapy

Published: July 24 1996

Category:Florida, Health, Research

GAINESVILLE—A 34-year-old Gainesville man was in good condition today (7/24) after becoming the first patient in Florida to undergo gene therapy to combat cystic fibrosis, the most prevalent lethal hereditary disease in America.

Bill Johnson underwent the 30-minute procedure Tuesday in the Clinical Research Center, a federally funded research facility at Shands Hospital at the University of Florida.

Cystic fibrosis, the so-called “thief of breath,” robs patients of life by slowly destroying their lungs through recurrent infections. Now UF researchers are studying the effectiveness of a novel method they hope will successfully transfer a normal copy of the cystic fibrosis gene into a patient’s airways.

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.

The experimental strategy relies on a new molecular “vehicle” known as the adeno-associated virus (AAV), which already enjoys a harmonious and symptomless existence in many humans. Scientists equip the virus with an important “passenger,” the healthy gene.

Physicians simply drip a single dose of the potion through a thin plastic tube into the patient’s nose, and through a fiber-optic bronchoscope into the lower right lobe of the lung.

Dr. Terence Flotte, a pediatrician, geneticist and microbiologist with UF’s College of Medicine — together with 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. The UF team is collaborating with Targeted Genetics and plans to test the treatment on five patients this year. Since November, seven patients have received the therapy, all at Johns Hopkins.

“This is the first trial in cystic fibrosis patients using this particular virus as a carrier,” said Flotte, who also co-directs the Gene Therapy Center at UF. “Previous attempts at gene therapy for cystic fibrosis were hampered because the viral vector caused a big inflammatory response. So far, none of our first seven patients in this study has shown any side effects, but they will be tracked for a year before we know for sure what the outcome will be. Our main purpose is to evaluate its safety for the lung and at its ability to correct the basic defect in cystic fibrosis.

“Cystic fibrosis is the single most common devastating genetic disorder in the U.S. population,” he added. “An estimated 30,000 Americans have it. It’s a logical target for gene therapy.”

Scientists will determine whether the gene is transferred successfully by brushing cells from the lining of the nose and lung to see if they have 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.

“We won’t know if this works for five years or so,” said Dr. Nicholas Muzyczka, the American Cancer Society Edward R. Koger eminent scholar at UF. “These are just the first attempts. But we are looking at something that may someday be as powerful as organ transplantation. This could become a major medical procedure that would allow us to do something about diseases we haven’t been able to fix so far.

“And if we can find a way to deal with this disease, we would have a tool in hand for dealing with other pulmonary diseases, such as emphysema or lung cancer.”

Credits

Writer

  • Melanie Fridl Ross

Category:Florida, Health, Research