Public Release: 

Novel gene therapy approach in 1st human trials

Cleveland researchers battle cystic fibrosis

University Hospitals of Cleveland

CLEVELAND, April 2, 2002: A 33-year old cystic fibrosis patient underwent the first gene therapy trial today using a novel approach to fight a deadly genetic disease that affects more than 30,000 Americans. The researchers include a team from The Research Institute of University Hospitals of Cleveland, its Rainbow Babies & Children's Hospital, Case Western Reserve University School of Medicine, and Copernicus Therapeutics Inc., developers of the novel gene transfer system.

"Over the last decade, there have been various attempts to transfer healthy genes into the cells of the airways of cystic fibrosis patients," explains primary investigator Michael W. Konstan, MD, Director of the LeRoy Matthews Cystic Fibrosis Center at Rainbow Babies & Children's Hospital, and associate professor of pediatrics at CWRU School of Medicine. "Most of these trials have involved the use of a viral vector, attaching the healthy gene to a virus that will invade cells. Unfortunately, the virus itself has caused troublesome inflammation in the study patients."

For more than a decade, UHC/CWRU researchers have explored alternative methods to viral vectors. Their work led to a patented approach produced by the Cleveland-based biotechnology firm, Copernicus Therapeutics, Inc. They developed a way to "compact" or tightly bind strands of DNA so that it is tiny enough to pass into the cell and then into the nucleus. Once inside a cell, researchers hope that the DNA will produce the normal version of the protein needed by cystic fibrosis patients.

Thirteen years ago, scientists discovered the cystic fibrosis (CF) gene. This defective gene upsets a delicate salt/water balance in the lungs. At the crux of the process is a protein, produced by the CF gene, which controls the flow of salt and water in and out of cells. In CF patients, this protein does not operate normally in the cells that line the airways. In turn, the airways accumulate thick and sticky mucus. Bacteria proliferate in the mucus and cause chronic infections that permanently damage lungs.

Under the direction of Dr. Konstan, the research team delivered the healthy gene into CF patient Robert Calhoun in a saline solution dripped slowly into his nasal passages. Investigators monitor the salt transport in his nose, called "nasal potential difference," as a barometer of the procedure's success. "CF patients have a markedly abnormal nasal potential difference," Dr. Konstan says. First, through biopsies of nasal tissue, researchers will determine whether the healthy gene was "taken up" by the cells. Then, if the DNA produces enough protein, there should be a change in the transport of salt and water in and out of the cells, which can be measured by the nasal potential difference test.

"This is a terrific example of the style of translational research that goes on at The Research Institute, bringing advances from the lab to improvements in health care", commented Huntington F. Willard, Ph.D., President and Director of the Research Institute of University Hospitals of Cleveland. "It also illustrates the strength of combining research efforts at the hospital, the university and industry. This kind of three-way collaboration is essential for transferring our discoveries to the public."

University Hospitals is the lead center for this study, and will enroll 12 patients with CF. The second site, Children's Hospital of Denver in Colorado, will send a team to Cleveland later in the spring to observe the procedures before they begin enrollment.

This DNA compaction technology was developed at Copernicus Therapeutics and is based on initial discoveries in the laboratory of Pamela B. Davis, MD, Ph.D., Director of the Willard A. Bernbaum Cystic Fibrosis Research Center and professor of pediatrics at Rainbow Babies & Children's Hospital and CWRU, and by Jose C. Perales, Ph.D., a former graduate student in the laboratory of Richard W. Hanson, Ph.D., professor of biochemistry at CWRU. Dr. Davis, Hanson and Perales are inventors of numerous patents assigned to CWRU School of Medicine. The study is funded in part by The Cystic Fibrosis Foundation.


University Hospitals Health System (UHHS) is the region's premier healthcare delivery system, serving patients at more than 150 locations throughout northern Ohio.

The System's 947-bed, tertiary medical center, University Hospitals of Cleveland (UHC), is the primary affiliate of Case Western Reserve University. Together, they form the largest center for biomedical research in the State of Ohio. The System provides the major clinical base for translational researchers at The Research Institute of University Hospitals of Cleveland, as well as a broad and well-characterized patient population for clinical trials involving the most advanced treatments. Included in UHC are Rainbow Babies & Children's Hospital, among the nation's best children's hospitals; Ireland Cancer Center, northern Ohio's only National Cancer Institute-designated Comprehensive Cancer Center (the nation's highest designation); and MacDonald Women's Hospital, Ohio's only hospital for women.

Committed to advanced care and advanced caring, University Hospitals Health System offers the region's largest network of primary care physicians, outpatient centers and hospitals. The System also includes a network of specialty care physicians, skilled nursing, elder health, rehabilitation and home care services, managed care and insurance programs, and the most comprehensive behavioral health services in the region.

CONTACT: Eileen Korey or Janice Guhl at 216-844-3825.

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