The Better Biomarkers of Acute and Chronic Allograft Rejection Project wishes to acknowledge the generous support and scientific collaborations of .......
December 6, 2004
New Test for Transplant
Rejection on the Horizon
Vancouver, BC - 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 fluids - can 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.
Note to Editors: Drs. Bruce McManus, Rob McMaster and Paul Keown, and a transplant patient are available for interviews about the Better Biomarkers Project on Friday, December 10, 2004 at the iCAPTURE Centre, St. Paul's Hospital.
Images and photographs available upon request.
Project background information described in the following 4 pages.
Gavin Wilson, Communications, Providence Health Care
Phone: 604-806-8583 Pager: 604-645-1190
Lisa Carver, Communications, Vancouver Coastal Health Research Institute
Phone: 604-875-3111 x 61777 / Cell 604-319-7533
Genome BC Project:
Better Biomarkers of Acute and Chronic Allograft Rejection
Patients with end-stage vital organ failure depend on transplantation to save their lives. But transplantation is far from failsafe. Because the process involves introducing a foreign organ into the recipient, the recipient's immune system may react to the new organ. Ironically, immune cells that protect the patient by recognizing, attacking and destroying foreign antigens like those of microbes can cause rejection and dysfunction in the very organ intended to save a patient's life. The Better Biomarkers of Acute and Chronic Allograft Rejection project will use the most advanced genomic, proteomic and bioinformatic tools to better understand this variation in order to produce an inexpensive, non-invasive and accurate test to determine whether rejection is occurring, and how a patient can expect their transplanted organs to perform. This research combines the knowledge of many of Canada's foremost experts in transplantation immunology, pathology, biochemistry, statistics, computer science and clinical care. The research team will focus in particular on patients who have undergone liver, heart or kidney transplants. Understanding the different responses patients have to immunosuppressive therapy will help physicians and nurses balance the necessity of the therapy with its possible side-effects. Personalized immunosuppressant therapy will not only alleviate patient discomfort and undesirable side effects, but also reduce the enormous economic burden of over-prescribing immunosuppressive drugs. And being able to monitor and predict rejection using a simple blood test will significantly reduce intrusive and expensive diagnostic procedures.
The Vancouver Coastal Health Research Institute (VCHRI)
The Vancouver Coastal Health Research Institute (VCHRI) is a joint venture in research between Vancouver Coastal Health and the University of British Columbia. It advances and promotes the development of all research activity across the health authority. VCHRI investigators are at the forefront of research activity. Through their leading-edge work, better health outcomes and healthier lives can and will be achieved. Major research areas include Clinical Epidemiology and Evaluation; Dermatology; ICORD (International Collaboration of Repair Discoveries - spinal cord injury research); Immunology and Infection including the Ike Barber Lab for Diabetes; musculo-skeletal research (bone health, arthritis, the Hip Health Centre); Neurological sciences including the Brain Research Centre, Mood Disorder Centre, and Pacific Parkinson's Research Centre; the Prostate Research Centre; and Respiratory and Critical Care.
For additional information please refer to the website:
The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research at St. Paul's Hospital
The iCAPTURE Centre builds on a 25-year legacy of health research begun by Drs. Jim Hogg and Peter Pare when they moved to Vancouver from McGill University in 1977. The iCAPTURE Centre now has 250 personnel, including 30 nationally funded principal investigators, and numerous trainees and staff members working to solve the unknowns of heart, lung, and blood vessel diseases. The Canada Foundation for Innovation (CFI), the BC Knowledge Development Fund and their partners have awarded over $20 million to the UBC-affiliated iCAPTURE Centre at St. Paul's Hospital for infrastructure. The purpose of the iCAPTURE Centre at St. Paul's Hospital is to link recent breakthroughs in genetic sciences and an understanding of multiple environments to abnormal gene expression and to changes in the structure and function (phenotype) of cells, tissues, and organs in model systems and in people at risk for or suffering from heart, lung, and blood vessel diseases.
For additional information please refer to the website:
The BC Transplant Research Institute
The BC Transplant Research Institute (BCTRI) was established in 2001, as a partnership between the BC Transplant Society and the BC Transplant Foundation. The Institute leads, coordinates, and supports transplant related research in BC. The research priorities of the Institute are presently in the areas of: basic science (immune tolerance) and experimental biology (organ preservation), clinical trials, epidemiology, ethics (living anonymous donation) and social sciences. The BCTRI works in collaboration with the BC Transplant Foundation and Michael Smith Foundation for Health Research. Between 1998 and 2003, the core researchers associated with the Institute received $8.3 million in grant funding, with nearly half coming from industry sources. These scientists have published over 100 peer-reviewed articles during this time.
For more information on the BC Transplant Society, Foundation and Research Institute, please visit:
www.transplant.bc.ca or call 1-800-663-6189.
Number of solid organ transplants
performed in BC in 2003
Number of Canadians Transplanted
Kidney130Kidney1,018 Liver35Liver376 Heart18Heart161 Pancreas-kidney5Pancreas33 Pancreas1Pancrease-Islet36 Pancreas-Islet7Single lung36 Single lung3Double lung98 Double lung3Other combinations55 TOTALS:202TOTALS:55
Vital organ failure is a leading cause of debility and premature death worldwide. Organ transplantation restores life and health to over 40,000 patients per year globally.
There is a chronic shortage of hearts, lungs, kidneys, livers and bowels for transplant in Canada as the need far outweighs the number of organs available for transplant. There are more than 3,500 people awaiting organ transplants in Canada, including more than 400 in BC. Since January 1986, when the BC Transplant Society was established, more than 2,500 organ transplant procedures have been performed in BC.
Organ rejection is the major cause of acute and chronic transplant injury and loss. Immunosuppressive drugs cause infection, cancer, diabetes, heart disease, and kidney failure. Transplant failure and treatment complications consume enormous health care resources.
Simple and accurate markers of immune status are urgently needed to optimize care, prevent transplant failure, minimize toxicity, and reduce costs.
The Better Biomarkers of Acute and Chronic Allograft Rejection project will determine hallmark genomic and proteomic biomarkers of rejection and accommodation in alloreactive, T-lymphocytes, blood serum and urine.
Goals: Better Biomarkers of Acute and Chronic Allograft Rejection Project
Evaluate the sensitivity, specificity, predictive value, cost-effectiveness and rapidity of throughput of these biomarkers in normal clinical practice
Employ these markers to individualize immunosuppressive treatment and identify novel targets for new drug development
Predict acute and chronic immune injury and the development of stable accommodation following solid organ transplantation
Prevent rejection-related injury or drug toxicity by informed and early adjustment of immunosuppressive treatment to maintain stable accommodation
Personalize drug therapy to optimize safety and efficacy guided by individual immune status, instead of present empirical treatment for all patients
Reduce costs of care, patient discomfort and debility, risk of graft injury and loss and development of a widely marketable test profile and identification of new biological targets
Bruce McManus, Providence Health Care (St. Paul's Hospital site) Investigator & Co-Director, The iCAPTURE Centre, St. Paul's Hospital Professor, Pathology, University of British Columbia
Paul Keown, Vancouver Coastal Health Research Institute (VGH site) Investigator, Immunology & Infection Research Centre, Vancouver Coastal Health Research Institute Head of Nephrology, Vancouver General Hospital; (VGH site) Professor & Director of Immunology/ Head, Division of Nephrology, University of British Columbia
Robert McMaster, Vancouver Coastal Health Research Institute (VGH site) Director, Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute Director, Transplant Immunology Research , BC Transplant Society Professor & Head, Department of Medical Genetics, University of British Columbia
For more information, visit the project's website at: