CF Gene Trials Show Promise for Other Diseases
from The Children's Hospital (TCH) News, April 2004
Gene therapy trials for cystic fibrosis at The Children’s Hospital and across the country show "unbelievable potential" for treating other genetic diseases, said Jeff Wagener, MD, professor of Pediatrics at UCHSC.
CF, a disease that affects 30,000 Americans, is caused by a defective gene that causes the body to produce an abnormally thick, sticky mucus that can lead to life-threatening lung infections. CF is currently treated with antibiotics and airway clearance, but once the gene that causes CF was identified in 1989, Wagener said, researchers began looking at how to fix or even replace that gene.
"Because there are more than 1,000 different gene variations in CF," he said, "it’s smarter to just replace the gene."
But the difficulty lies in how to transfer the gene into the lungs, Wagener said.There are several transfer techniques — or "vectors" — being tried, including breathing a virus or compacted DNA into the lungs. Cleveland-based biotechnology firm Copernicus patented a way to "compact," or tightly bind, strands of DNA so they are tiny enough to pass through a cell membrane and into the nucleus.
TCH and the University of Colorado Health Sciences Center, one of the largest CF care centers in the country, have completed two gene therapy trials for CF and are enrolling patients for a third. Results from the first two studies have been encouraging, Wagener said.
In the first three-month trial, 10 patients at TCH and more than 40 nationwide were dosed with an adeno-associated (AAV) virus that contained a new gene.
The problem with the virus vector, Wagener said, is that the patient’s body attacks the virus.
The second study used compacted DNA. In this study, doctors delivered the healthy gene in a saline solution dripped into patients’ nasal passages to see if the gene got into those cells. Nine of 12 patients nationwide and three at TCH showed evidence the gene was working, Wagener said.
"The results were as encouraging as the AAV trial," Wagener said.
TCH has enrolled three patients in yet another AAV trial and expects to enroll an additional seven to nine subjects by August.
The encouraging results from these trials show promise for all genetic diseases, Wagener said, including sickle-cell anemia, diabetes, hypertension, muscular dystrophy and perhaps even obesity.
"It’s conceivable that when you get a bacterial infection in the future we could just give you another gene instead of an antibiotic to fight off infection," he said. "It may go well beyond treating genetic diseases. The ultimate potential is unbelievable."
