UF and UM Earn $10.4 Million for New Gene Therapy Initiative in Diabetes
Miami, FL (December 13, 2000) -- Armed with a $10.4 million grant from the Juvenile Diabetes Research Foundation International, University of Florida and University of Miami researchers announced today they will launch a new center devoted to the study of gene therapy to fight diabetes and its complications.
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 plan represents a pivotal shift in the traditional approach to diabetes research and a refocusing of scientific strategy. UF and UM scientists 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 simply treating ailments attributed to single gene defects. Diabetes, in fact, is thought to be caused by a constellation of genes that interact with unknown environmental forces.
“The center will join with the JDRF’s mission to find a cure for diabetes,” said center Director Mark Atkinson, Ph.D., 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 feel we have a very ambitious set of investigators who can tackle that lofty goal.”
"The University of Florida is on the cutting edge of the development and application of gene therapy, and the University of Miami's Diabetes Research Institute is a leader in islet isolation and transplantation. 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," said center Co-Director Camillo Ricordi, M.D., 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 University of Miami will receive slightly over $1 million of the total award. Type 1 diabetes occurs when white blood cells vital to the body’s defenses against infectious diseases launch a self-directed attack on insulin-producing beta cells, situated inside structures known as islets found in the pancreas.
The insulin these beta cells produce regulates how the body uses and stores sugar and other food nutrients for energy. More than 750,000 Americans battle the disease. Many suffer major complications, including damage to blood vessels, which can lead to heart disease, stroke, blindness, kidney failure, and poor limb circulation. Researchers have found that 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. “I’ve been working in diabetes research for 17 years, and my focus has been on prediction, pathogenesis and prevention,” Atkinson said.
“I’m still active in that arena and progress has occurred, but about year-and-a-half ago, having seen what the gene therapists here were able to do with gene transfer, I just became convinced this is something that, if investigated correctly, could revolutionize diabetes treatment. So I’ve switched, almost overnight, half my research efforts toward this avenue because I think it holds such promise to make an impact sooner, rather than years from now.”
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, whose potential was first recognized by Kenneth L. Berns, M.D., dean of UF’s College of Medicine. Berns is a co-investigator on one 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 vectors. That means it could yield longer-lasting effects.
“Gene therapy has been held as a revolutionary promise for medicine for a couple decades now, and as we look back many people may have thought there was more hype than actual benefit,” Atkinson said. “Now, as we look back, AAV is a story that with time has just grown better.”
The initiative unites scientists from UF's Genetics Institute and its Center for Immunology and Transplantation together with UM's Diabetes Research Institute. 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 for specimen analysis all will be housed at UF; an islet and kidney transplantation core will be at the University of Miami.
The center’s key initiatives focus on 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 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 and to improve cells' defense mechanisms.
Patients with diabetes who undergo kidney transplant are prone to complications when certain cells in the organ begin to proliferate wildly, eventually clogging the kidney and shutting it down. Previous research has shown that the blood protein angiostatin can prevent cell overgrowth. Researchers will use AAV to insert the gene that codes for the protein into key cells in the rat kidney during transplantation, with the aim of preventing kidney failure and dramatically prolonging the life of the transplanted organ.
Scientists will continue efforts 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 by using gene therapy to block the formation of excess blood vessels 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 the research being done on diabetes, particularly in the area of genetics and immunology. And the same thing is true with the use of AAV as a vector for gene therapy.”
Mitra Zehtab, MD, MBA