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.
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 at the iCAPTURE Centre, St. Paul’s Hospital.
Images and photographs available upon request.
Background
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: www.vchri.ca.
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: www.icapture.ca.
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.
Transplantation facts
Number of solid organ transplants performed in BC in 2003:
Kidney
