Jan. 24, 2005 VANCOUVER – Researchers at St. Paul’s Hospital and Vancouver General Hospital are developing a revolutionary new test to diagnose and facilitate treatment of organ rejection in transplant patients.
The $9.1-million Vancouver-based study, called Better Biomarkers of Acute and Chronic Allograft Rejection Project, led by Drs. Bruce McManus, Paul Keown and Rob McMaster, is jointly funded by Genome Canada, Genome BC, Novartis Pharmaceuticals and IBM. The project is believed to be the largest study of its kind ever performed in Canada and will focus on patients who have undergone liver, heart and kidney transplants.
The project leaders will make a plenary presentation about their work at the eighth annual British Columbia Transplant Research Day, to be held Thursday, December 9, 2004 at the Chan Auditorium, Children’s and Women’s Health Centre of BC.
Patients with end-stage vital organ failure depend on transplantation, but the process has its remaining challenges. Immune cells that normally protect patients can cause rejection and destruction of the very organ intended to save their life. To test for rejection, patients must undergo uncomfortable and invasive biopsies. Patients must also take drugs that inhibit rejection by suppressing the immune response, and which can have serious side effects.
Project researchers seek to define which biomarkers—for example, substances found in the blood or other body fluids¾can be used as a diagnostic and prognostic test for organ rejection and immunosuppressive therapy response. Being able to monitor and predict rejection using a simple blood test will significantly reduce intrusive and expensive diagnostic procedures.
“One of the major problems facing clinical caregivers in the management of organ rejection is determining whether a transplanted organ is undergoing rejection,” says Dr. Bruce McManus of the James Hogg iCAPTURE Centre, based at St. Paul’s Hospital, and co-leader of the project. “Most of the current methods for detecting rejection require tissue biopsies. These procedures may cause emotional and physical discomfort to patients and may result in findings that are inconclusive.”
Project co-lead Dr. Paul Keown of the Vancouver Coastal Health Research Institute, VGH site, says, “In order to prevent organ rejection, powerful drugs are used to suppress a patient's immune system. Such therapies reduce the probability that the patient's own body will attack the transplanted organ, but impairing the immune system may leave the patient susceptible to infections and malignancies, and may damage the precious transplanted organs.”
Individual patients vary in their response to immunosuppression therapy. It is this variation that project researchers, using the most advanced genomic (study of genes), proteomic (study of proteins) and bioinformatic (information science) tools available, will seek to better understand.
“These new tools are critical in order to produce an affordable, accurate, and widely useful test to determine whether rejection is occurring and how a patient’s transplanted organ is faring,” says Dr. Rob McMaster, project co-lead, Director of the Immunity and Infection Research Centre at the Vancouver Coastal Health Research Institute, and Director of Transplant Immunology Research for the BC Transplant Society.
Understanding the different responses patients have to immunosuppressive therapy will also help physicians balance the necessity of the therapy with its possible side effects. Personalized therapy could help reduce the enormous economic burden of over-prescribing immunosuppressive drugs.
All three co-leaders of the Better Biomarkers of Acute and Chronic Allograft Rejection Project are faculty members at the University of British Columbia. This project is funded for three years by Genome Canada through Genome BC and private sector partners Novartis Pharmaceuticals and IBM. Other partners include Providence Health Care, the Vancouver General Hospital Foundation, St. Paul’s Hospital Foundation, UBC, Genome BC, the James Hogg iCAPTURE Centre, BC Transplant Research Institute and Affymetrix.
The research team includes international leaders in transplantation immunology, pathology, biochemistry, genomics, proteomics statistics, information science and clinical care.
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