Reaping the rewards of Biomarker Discovery
→our 2nd report to stakeholders, 2010-11
Message from the Director
Bruce McManus
MD, PhD, FRSC, FCAHS
A Physician's Viewpoint
Andrew Ignaszewski
MD FRCPC
A Patient's Viewpoint
Vivianne Toupin
With several biomarker initiatives underway in heart, lung and kidney failure, the PROOF Centre is now in the process of moving from theory to practice. Very real advances have been made in the validation of transplant rejection biomarker sets, with new blood tests expected to be trialed in the clinic next year. We have early data suggesting biomarkers that reflect progression of kidney disease and resolution of congestive heart failure, and will soon have developments on biomarkers for COPD exacerbation.
Collaborations are the heart of the PROOF Centre and are the reason for its continued success and growth. From the patients willing to be engaged in research such that others might benefit from their experience, to the healthcare professionals and administrators who are instrumental in ensuring new discoveries are implemented into the system.
Our collaborations with individuals, groups and organizations span geographical, institutional and disciplinary boundaries – all working towards a common goal of developing new solutions for heart, lung and kidney diseases.
Our progress, track record and unique business development model has attracted technology-oriented-business partners who have recognized the PROOF Centre’s potential as an excellent biomarker discovery collaborator.
Our next challenge is to translate our scientific insights into new clinical approaches for the management of patients with heart, lung, and kidney disease.
To that end, we are engaged in discussions with both diagnostic and pharmaceutical companies to partner clinical testing and development of our emerging biomarker panels. Completion of these business partnerships will be integral to bridging the gap between our discoveries and routine clinical use of new diagnostic tools.
This report highlights our research progress and some of the outcomes of our current academic and commercial collaborations. We anticipate being able to announce several more partnerships in the very near future.
We are gratified by the progress made in all fronts in our research and organization thus far.
The next year will be about continued growth of new programs, bringing our major biomarker initiatives to fruition and ensuring the further development of the PROOF Centre as a self-sufficient research organization dedicated to improving the quality of health care for Canadians and all sufferers from heart, lung and kidney diseases worldwide.
George Schreiner MD, PhD
Chairman of the Board, PROOF Centre of Excellence
(Expressed in thousands of Canadian dollars)
March 31, 2011, with comparative figures for 2010
| 2011 | 2010 | |
|---|---|---|
| Assets: | ||
| Current assets: | ||
| Cash and cash equivalents | 1,100 | 7,585 |
| Short-term investments | 7,523 | 5,200 |
| Interest receivable | 13 | 117 |
| Accounts receivable | 61 | 65 |
| Prepaid expenses and deposits | 1,050 | 562 |
| 9,747 | 13,529 | |
| Capital assets, net of accumulated amortization of | ||
| $2,168 (2010 - $1,295) | 603 | 631 |
| 10,350 | 14,160 |
| Liabilitites and Net Assets: | ||
| Current liabilities: | ||
| Accounts payable and accrued liabilities | 125 | 877 |
| Deferred operating contributions | 9,300 | 12,138 |
| Deferred capital contributions | 548 | 574 |
| Net assets: | ||
| Unrestricted | 322 | 514 |
| Invested in capital assets | 55 | 57 |
| 377 | 517 | |
| 10,350 | 14,160 |
(Expressed in thousands of Canadian dollars)
Year ended March 31, 2011, with comparative figures for 2010
| 2011 | 2010 | |
|---|---|---|
| Revenue | ||
| Amortization of deferred operating contributions | 3,605 | 2,599 |
| Amortization of deferred capital contributions | 823 | 950 |
| Unrestricted contributions | 974 | 1,118 |
| Interest income | 134 | 215 |
| Unrealized gain on investments | 10 | - |
| 5,546 | 4,882 | |
| Expenses: | ||
| Core facilities (biomarkers program) | 3,286 | 2,154 | Materials and supplies | 1,243 | 1,356 |
| Equipment | 127 | 60 |
| Administrative salaries | 346 | 325 |
| Administrative operations | 108 | 199 |
| Hosting conferences | 53 | 17 |
| Attending conferences | 153 | 133 |
| Other knowledge dissemination | 53 | 70 | Other commercialization | - | 12 | Market studies and business development | 152 | 105 |
| Intellectual property | 218 | 199 |
| Space improvements | 1 | 30 |
| 5,740 | 4,660 | |
| Excess (deficiency) of revenue over expenses | 194 | 222 |
(Expressed in thousands of Canadian dollars)
Year ended March 31, 2011, with comparative figures for 2010
| 2011 | 2011 | Cash provided by (used in): |
|---|---|---|
| Operations: | ||
| Excess (deficiency) of revenue over expenses | (194) | 222 |
| Amortization of capital assets | 873 | 998 |
| Amortization of deferred capital contributions | (823) | (950) |
| Unrealized gain on investments | (10) | - |
| (154) | 270 | |
| Changes in non-cash operating items: | ||
| Interest receivable | 104 | (4) |
| Accounts receivable | 4 | (45) |
| Prepaid expenses and deposits | (488) | (369) |
| Accounts payable and accrued liabilities | (752) | 673 |
| Deferred operating contributions | (2,838) | (1,853) |
| (4,124) | (1,328) | |
| Investments: | ||
| Additions to capital assets | (48) | (48) |
| Additions to short-term and long-term investments | (2,313) | (200) |
| (2,361) | (248) | |
| Decrease in cash and cash equivalents | (6,485) | (1,576) |
| Cash and cash equivalents, beginning of year | 7,585 | 9,161 |
| Cash and cash equivalents, end of year | 1,100 | 7,585 |
| Supplemental information: | ||
| Cash received for interest | 238 | 211 |
| Non-cash transactions: | ||
| In-kind donation of capital assets | 797 | 834 |
George Schreiner,
Board Chair and Chief Executive Officer, Cardero Therapeutics
Donald Brooks,
Associate Vice President Research, University of British Columbia
Lynda Cranston,
President and CEO, Provincial Health Services Authority
Katherine Gibson,
President and Founder, Helio Consulting
Frank Holler,
Chief Executive Officer & Partner, Lions Capitol Corporation
Seigo Izumo,
Independent Consultant
Heather Manson,
Director, Ontario Agency for Health Protection and Promotion
Bruce McManus,
Director, PROOF Centre of Excellence
Bruce Milley,
President, MJC Business Services Inc
Volker Pfahlert,
Independent Consultant, Former Head, Roche Centralized Diagnostics
Bernard Prigent,
Vice President & Medical Director, Pfizer Canada
Richard Rees,
CEO, Institute of Chartered Accountants of BC
Carl Roy,
Senior VP, Provincial Health Services Authority, and Executive Officer, Emergency Health Services Commission and the BC Ambulance Service
This is the lead program of the PROOF Centre, wherein we work towards replacing tissue biopsies with non-invasive blood tests that diagnose and predict rejection and related organ failure. Beginning in 2004 with funding from Genome Canada and a range of partners, the team has discovered blood-based gene and protein marker sets that predict and diagnose acute and chronic rejection in heart and kidney transplant patients. The team has been busy refining these blood tests, moving them onto instruments that can be used in a hospital laboratory, and running an international observational trial where patients are enrolled and their blood is banked for assessment of assay performance. The data will be submitted to regulatory agencies and health care systems for clinical implementation.
COPD is a progressive, epidemic lung disease that leads to poor quality of life and productivity. Patients are routinely under-diagnosed because of poor diagnostics. Patients with COPD can have frequent exacerbation episodes of COPD wherein hospitalization and additional drugs are needed, or very few such episodes. The goal of this program is to identify sets of blood-based gene and protein biomarkers that allow a physician to determine who will undergo frequent exacerbation episodes and who will not, thus allowing more effective management and reduced hospital visits and costs.
The PROOF Centre has partnered with GlaxoSmithKline (GSK) in this key biomarker program. GSK is providing patient samples and thorough phenotypic from a large cohort collected with the idea of solving challenges in COPD. The PROOF Centre is now running discovery assays (genes on Affymetrix microarrays and proteins by mass spectrometry) on 304 carefully selected patient samples including patients with COPD and those who do not have COPD. Discovery biomarker panels will be validated in a separate set of patient samples later in 2011.
CHF is a progressive disease arising when the heart is unable to fill with blood (diastolic failure) and/or pump (systolic failure) blood sufficiently. While different management strategies are required for each condition, current diagnostic tools, beyond ultrasound in specialists’ hands, are unable to differentiate systolic and diastolic heart failure. The PROOF Centre is working to develop blood biomarker tests to distinguish diastolic from systolic heart failure. Such tests will guide clinicians in selecting the most appropriate therapy for individual patients regardless of their geographical remoteness or their specialty training.
The current program builds on our collaboration with Alberta HEART (www.albertaheartresearch.ca), a transdisciplinary team funded in Alberta focused on the recruitment and evaluation of patients with heart failure. Samples from patients enrolled in Alberta HEART will be used to discover genes and proteins in the blood that diagnose heart failure and distinguish the two main types of heart failure.
The program also includes a collaboration with the Canadian Heart Failure Network (www.chfn.ca), a not for profit academic collaboration of Canadian HF specialists with a large prospective HF patient database derived from more than 20,000 patients across Canada. Patients will be enrolled in the CHFN for use in the validation phase of this program in early 2012.
Chronic Kidney Disease (CKD) patients can experience a range of possible disease outcomes; however, physicians currently have limited ability to predict individual patient outcomes and to treat them accordingly. The PROOF Centre is discovering and developing panels of blood biomarkers aimed at developing tools to assess the likelihood of progression of CKD in individual patients. The team has identified blood-based gene and protein biomarkers of CKD progression from a local cohort of 84 patients that distinguishes patients with slow and rapid disease progression. These results were presented at three national and international conferences in early 2011.
Our next steps include exploring the effectiveness of combining these genes and proteins with clinical/demographic data to better predict CKD progression. We then plan to validate selected blood-based gene and protein biomarker panels in a separate set of patients after the final biomarker panels are decided upon.
Recovered Heart Function is achieved in many heart transplant recipients. In the heart transplant setting, patients have end-stage heart failure before transplantation, and after receiving the new heart their heart function recovers. This post-transplant heart function recovery can serve as a model for studying blood-based genes and proteins that indicate heart function recovery after drug therapy in patients without a heart transplant. Using blood from end-stage heart failure patients, individuals with normal heart function, and stable heart transplant patients, the team identified genes and proteins that normalize one month after heart transplant and remain normal throughout the first year post-transplant. By focusing on these genes and proteins, we discovered that a subset of these can serve as biomarkers of recovered heart function. These blood genes and proteins will be tested on blood from patients who were enrolled in our study at the St. Paul’s Hospital Heart Maintenance Clinic.
New Biomarker Technology is needed for improved biomarker monitoring. The PROOF Centre is working with the UVic Genome BC Proteomics Center in developing and validating a blood test with more than 150 proteins that can be run a very small amount of blood. This test, called Multiple Reaction Monitoring (MRM), will be used to risk stratify patients with heart, kidney, and eventually, lung disease with improved specificity and sensitivity and decreased cost.
Acute Chronic Heart Failure is a life-threatening condition characterized by inadequate cardiac output, blood pressure instability, and often, heart rhythm disturbances. AHF patients may develop persistent, or chronic, heart failure, and progress to require mechanical ventricular assist devices or cardiac transplantation, or even face death. The PROOF Centre is seeking markers that forecast the course of such profoundly ill patients and help to guide early care decisions by specialist clinicians.
This year we will be entering the third phase of our Biomarkers in Transplantation program (BiT3). This phase involves bringing our new blood tests into the hospital clinics to help doctors diagnose organ rejection after transplant. Next year we plan to working directly with doctors and their transplant care teams within clinics at St. Paul’s Hospital in Vancouver, BC, through the actual use of the new, validated and useful biomarker tests to optimize management for their patients.
The PROOF Centre believes that imparting knowledge and continuous learning in a stimulating and supportive environment contributes to the sustainability and amplification of its programs. The strategic focus of the PROOF Centre, biomarker development and Implementation, is a new and challenging arena. From visiting scholars, to postdoctoral fellows, graduate students, and undergraduate students, the PROOF Centre provides its inquirers and trainees with in depth skills and experiences that span the biological, technological and computational sciences, business, societal considerations and more – all vital pieces of a biomarker puzzle we are determined to solve. Our trainees include Senior Biomarker Development Fellow, Rhonda Wideman, who manages biomarker discovery and development activities, and Doctoral Graduate Student Zsuzsanna Hollander who is focused on identifying biomarkers of recovered heart function using data collected in the Biomarkers in Transplantation (BiT) project. Other extraordinary trainees are pushing the boundaries of knowledge with a passion for better health care, Post-Doctoral Fellows (Drs. Agnieszka Klimek, Heesun Shin, Yi Yang), Graduate Students (David Lin, Anna Meredith), and Undergraduate Students (Casey Shannon, Marc Irawan, Keerat Sidhu).