Juvenile Diabetes Research Foundation Awards $10.4 Million Grant To Create New Center For The Study Of Gene Therapy And Diabetes At UF

December 13, 2000

GAINESVILLE, Fla. — Armed with a $10.4 million grant from the Juvenile Diabetes Research Foundation International, University of Florida researchers announced today (12/13) they will launch a new center devoted to the study of gene therapy to fight diabetes and its complications.

The plan represents a pivotal shift in the traditional approach to diabetes research and a refocusing of scientific strategy. UF scientists — along with colleagues at the University of Miami — will capitalize on gene therapy’s potential to deliver medicine in novel ways, engineer rejection-proof tissues for islet and kidney transplant, and tackle diabetes-associated complications such as vision loss.

The approach is a move away from using gene therapy to treat ailments caused by a single gene defect. Diabetes is thought to be caused by a constellation of genes interacting with unknown environmental factors.

The facility will be known as the JDRF Gene Therapy Center for the Prevention of Diabetes and Its Complications at the University of Florida and the University of Miami. The grant is the largest the diabetes association has awarded an academic institution for the study of gene therapy.

“The center will join in the JDRF’s mission to find a cure for diabetes,” said center Director Mark Atkinson, the S. family/American Diabetes Association professor for diabetes research at UF’s College of Medicine. Atkinson also directs UF’s Center for Immunology and Transplantation. “It’s a very ambitious goal, but we have a very ambitious group of investigators to tackle that lofty objective.”

UF has a strong record in the development and application of gene therapy, while the University of Miami’s Diabetes Research Institute is a recognized leader in islet isolation and transplantation, said center Co-Director Dr. Camillo Ricordi. Ricordi is the Stacy Joy Goodman professor of surgery and medicine at the University of Miami School of Medicine and scientific director of its Diabetes Research Institute.

“The joining of our teams in this critically important and timely initiative will result in a major synergistic force toward the development and application of novel treatments for patients with diabetes,” Ricordi said.

Type 1 diabetes occurs when white blood cells vital to the body’s defenses against infection attack insulin-producing cells situated inside structures known as islets, which are found in the pancreas. Insulin regulates how the body uses and stores sugar and other food nutrients for energy. People with type 1 diabetes must take insulin injections daily.

More than 1 million Americans battle the disease. Many suffer major complications, including damage to blood vessels, which can lead to heart disease, stroke, blindness, kidney failure and amputation of the lower limbs.

“Diabetes is a devastating and unpredictable disease, and insulin is an imperfect form of life support,” said Peter Van Etten, president and chief executive officer of the JDRF. “Every person affected by diabetes lives with the constant threat of developing complications. If the researchers at our new center are successful, and we are very encouraged that they will be, it will make a critical difference to those suffering from this disease.”

Researchers have found the destructive autoimmune process smolders for years before symptoms flare. That quirk could be diabetes’ Achilles’ heel: The long period prior to the onset of symptoms provides an opportunity for interventions aimed at preventing the disease’s development.

“Despite having spent 17 years investigating the cause of diabetes, I recently shifted half of my research efforts to gene therapy,” Atkinson said. “This could revolutionize diabetes treatment and may make an impact sooner, rather than years later.”

In particular, UF researchers hope to capitalize on the promise of the adeno-associated virus, or AAV, a means of delivering corrective genes to cells. Its potential was first recognized by Dr. Kenneth L. Berns, dean of UF’s College of Medicine and vice president for health affairs

at UF’s Health Science Center. Berns is a co-investigator on two of the center’s six planned projects. AAV is especially promising because it appears to infect cells without producing side effects, and the body’s immune system does not attack it as powerfully as it assails other gene therapy vectors. That means it could yield longer-lasting effects.

The initiative unites scientists from seven UF departments and two centers, the UF Genetics Institute and UF’s Center for Immunology and Transplantation. Six primary research studies and four pilot projects are planned. The center also will feature four core facilities: an administrative core, a core that manufactures the AAV vector for all investigators and a third that will analyze of specimens, all at UF; and an islet and kidney transplantation core at the University of Miami. The center’s key initiatives — which will focus initially on animal studies, then move to trials in people — include the following:

Researchers have long attempted to restore normal insulin production in patients by transplanting healthy islets from donors. But islet cells are particularly vulnerable to renewed attack by the immune system and to damage by “anti-rejection” drugs. Two center projects will focus on genetically modifying islet cells in the laboratory to prevent the immune system from attacking transplanted cells or to improve cells’ defense mechanisms.

Patients with diabetes who undergo kidney transplantation are prone to complications when certain cells in the organ proliferate wildly, eventually clogging and shutting down the kidney. Researchers will use AAV to insert a gene that may prevent this overgrowth, with the aim of preventing kidney failure and dramatically prolonging the life of the transplant.

Scientists will seek to alter AAV’s molecular coating to improve its ability to transmit genes into islet cells. They also will try to combat diabetes-related blindness, using gene therapy to block excess blood vessel formation in the retina.

“This grant is a reflection of our success and represents a very nice coming together of two independent areas of research and technology,” Berns said. “We have achieved significant recognition with respect to our diabetes research, particularly in the areas of genetics and immunology. And the same thing is true with the use of AAV as a vector for gene therapy.”