General and inexpensive saliva-based viral RNA testing by direct imaging

In the absence of a vaccine and/or effective treatment, rapid and robust testing is vital not only to reduce the transmission and spread of SARS-CoV-2, but also for paving the way to safely reopen borders and reinstating the world economy. Most Covid-19 tests are performed using nasopharyngeal swabs that are sent to a hospital or public health laboratory to be processed for RT-PCR analysis using expensive equipment by technically trained staff. The specificity of such amplification-based tests makes them superior to many other detection tests. However, the occurrence of false-negative results due to the low levels of viral RNA found in such samples, as exemplified by recent problems with Spartan Cube1, suggests that avoiding nucleic acid amplification entirely and switching to the direct detection of viral RNA could be highly advantageous for SARS-CoV-2 detection.

Funded by the CIHR Rapid Research Opportunity and MSFHR, Dr. Peter Unrau is leading a team of researchers to develop a new saliva-based viral testing strategy for use in the current Covid-19 pandemic. Dr. Unrau (professor in RNA biochemistry) and co-investigator Dr. Forde (professor in biological physics) will coordinate a research team at Simon Fraser University. They will work in collaboration with David Rueda, a professor in single-molecule imaging at Imperial College London.

This COVID-19 research will allow the development of a fast, inexpensive and sensitive viral RNA test that, in principle, could be used for point of care testing at home. The proposed SARS-CoV-2 RNA single-molecule imaging test will be highly specific, will rely on simple well-understood chemistry, and will include an inexpensive imaging device that connects to a cell phone. An additional benefit of this device is that test procedures can easily be adapted for the screening of other RNA pathogens in the future.

Funding Competition: CIHR Operating Grant: COVID-19 Rapid Research Funding Opportunity – Diagnostics

Funders: CIHR; MSFHR

Automated body composition analysis for precision medicine applications

There is growing evidence showing that the amount of muscle and fat one has in the body influences various aspects of cancer such as carcinogenesis (formation of cancer), response to chemotherapy drugs (to decide on the optimal dosage to the patient to destroy cancer cells while avoiding damage in other organs), death resulting from complications due to surgery, and overall survival outcomes. Conversely, cancer also causes loss of muscle mass. Accurate and easily available tools are thus needed to measure muscle and fat in an individual in the context of cancer treatment decisions. CT images are almost universally acquired in cancer diagnosis and treatment planning, and these directly show muscle and fat in the body. But in order to extract measurements, manual intervention (which is tedious) or automated tools are needed. We are developing a fully automated 3D method to measure the amount of muscle and fat from 3D CT images available in the cancer clinic. The availability of these measurements will enable correct chemotherapy treatment dosage to be determined for each individual based precisely on their body composition, resulting in better health outcomes.

Multispectral RNA Mango: Synthesis of new multicolour fluorogens for incorporation into pathogen detection and identification kits

With the increasing prevalence of viral pathogens as exemplified by COVID-19, reliable and inexpensive detection is of increasing importance. Rapid testing allows appropriate and immediate treatment, which can have a profound effect on the treatment outcome. Early on-site detection is also greatly beneficial for hospitals and clinics since it would allow patients to be rapidly screened before entering the system.

Viruses and bacteria contain unique RNA fingerprints that can be used to identify their exact species. Recently, we have developed RNA Mango technology that can specifically and rapidly detect extremely low levels of RNA and that outcompetes the previous standard for RNA-based pathogen detection (RT-PCR) in terms of speed, while maintaining sensitivity. A limitation of our current technology is that it is not yet as reliable as it needs to be, since it is lacking controls for reaction failure — an important aspect for pathogenic detection and identification. In this application, we will further develop our RNA-detection technology into a rapid, multichannel, colour-based test that will allow us to quickly and reliably detect and identify multiple pathogens and expand its commercial in vivo applications.

Fucosylation inhibitors for convenient production of fucose-deficient antibodies

Therapeutic antibodies have revolutionized the treatment of cancers. The efficacy of many of these antibodies depends on their ability to recognize and bind to cancer cells. These antibodies then recruit immune cells to kill the cancer cells. Recent interest has focused on the different sugar molecules attached to the antibody and their role in helping or hindering the recruitment of immune cells. Specifically, eliminating one specialized sugar known as fucose from antibodies dramatically improves their ability to recruit immune cells and kill cancers. Industry is therefore interested in ways to prevent this sugar modification and to thereby produce improved anti-cancer antibodies.

We have developed a new family of chemical compounds that block the addition of fucose onto antibodies as they are being produced. We now aim to translate this work to drive the generation of improved therapeutic antibodies. Because the fucose-deficient antibodies are much more potent, it is expected that lower doses of these antibodies can be used leading to a lowered risk of side effects. Additionally, the increased potency should lead to improved efficacy of therapeutic antibodies and outcomes for cancer patients in British Columbia and elsewhere.

Design and evaluation of an evidence-based exercise program to enhance protective responses for avoiding fall-related traumatic brain injury in older adults

Falls cause up to 80% of traumatic brain injuries (TBI) in older adults. Any fall from standing may cause TBI if head impact occurs. Humans use movement strategies to avoid head impact during falls, such as 'arresting' the fall with the arms. Through video capture of real-life falls, we found that these strategies persist but become less effective for older adults in long-term care, with over 1/3 of falls resulting in head impact in this setting. This project continues our work with Debbie Cheong (Osteofit Provincial Coordinator at BC Women's Health Centre) to design and evaluate novel exercise programs for enhancing protective responses for avoiding head impact in falls. We will identify the strength and flexibility demands of common safe landing strategies observed in falls in older adults, and design and evaluate feasible approaches to enhance those capacities for older adults of varying physical and cognitive status.

This project will lead to new evidence on the strategies that older adults use to avoid head impact during falls, and the musculoskeletal demands of those strategies; new exercise-based approaches for targeting and enhancing the effectiveness of fall protective responses in older adults; and evidence of the feasibility and effectiveness of our exercise program for older adults.

Value Judgments in Health Economics Modelling for Primary Care: Towards Patient and Public Partnership in BC

In scientific research, many decisions are needed. Some take scientific expertise, but others take knowing what people find important. Such 'value judgments' include: choosing a topic and how to study it, setting goals, and deciding how to share results.

Patients and the public can inform value judgments in research by being partners and sharing what is most important to them, including

  1. what is most important to know;
  2. what errors are most important to avoid.

This is necessary in health economics, the type of research that looks at health and costs as part of healthcare planning. This project will build on a study that asked health economists about value judgments, including whether and how value judgments in their studies could affect healthcare. In a new project, researchers will start a conversation with patients and the public about the same issue. First, they will create short videos about value judgments in research, including how health economists think about and manage them in their studies. Then, patients and the public who viewed the videos will be asked what they think. Could health economists do a better job of managing value judgments?

The study will help make sure health economics research in BC is clear, understandable, and done in partnership with patients and the public. It will help ensure that British Columbians' values are front and centre in research, including where to focus and how to manage possible errors in studies about healthcare.

Strengthening primary care through population-based research

Primary care includes the day-to-day services provided by family doctors, nurse practitioners, and other health care providers. High quality primary care that follows patients over time and coordinates specialist and hospital care is key to an effective and efficient health care system. Unfortunately, many Canadians struggle to get primary care where and when they need it, despite there being more family doctors per person than ever before.

My research program seeks to answer the following questions:

  1. How can we make sure we have the right number of health care providers to meet the needs of Canadians now and in the future?
  2. How can we efficiently organize delivery of primary care to meet the needs of patients? How do we improve access to effective care for underserved groups, including people managing both mental and physical health conditions and recent immigrants and refugees?

I analyse routinely collected data from health care delivery and look at the impact of policy changes using statistical models. I work in partnership with researchers who have complementary skills collecting information through interviews and focus groups. My research teams include patients, care providers, and people who plan health services.  This helps make sure we ask questions that matter and that research results will help change our health care system.

What are the impacts of being formally enrolled with a GP on continuity and integration of care? Evidence from a comparison of Quebec and British Columbia

MSFHR is providing matching funds to support Kimberlyn McGrail’s and Laurie Goldsmith’s BC-based research activity as part of the Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research (SPOR) Network in Primary and Integrated Health Care Innovation (PIHCI) initiative. The BC/Quebec research team was funded through a SPOR PIHCI Provincial/Territorial Comparative Program and Policy Analysis Grant, with additional funding from the University of British Columbia and several Quebec-based institutions and organizations.

The idea behind patient enrolment with a general practitioner (GP) — also called rostering or registration — is that all patients have a family doctor responsible for their care. For some provinces, patient enrolment is a foundation of efforts to make primary health care more accessible, continuous, and of higher quality. Many jurisdictions either have or are considering implementing such programs, with the belief that this can ensure accessible, timely health care for Canadians. To date, little is known about the actual benefits of patient enrolment policies in Canada.

Researchers in two provinces with patient enrolment programs — British Columbia and Quebec — have teamed up to investigate and compare the impact of different approaches to enrollment with a GP on the continuity and integration of care for patients in each province.

Dr. Kimberlyn McGrail, associate professor at the University of British Columbia (UBC) in the School of Population and Public Health, and the Centre for Health Services and Policy Research, is leading the BC team of researchers. The Quebec-based research is led by the project’s overall principal investigator Dr. Erin Strumpf, associate professor in the Department of Economics and the Department of Epidemiology, Biostatistics and Occupational Health at Montreal’s McGill University.

The two-year project brings together patients, health care providers, decision makers and researchers. Researchers will interview patients and family doctors on their experiences and priorities regarding enrolment and will analyze health care data to assess the effects of enrolment policies on health care services use.

The research results will provide insights on the effects of enrolment, including whether it is more effective for some patients than others, with special attention paid to those Canadians who use and need the health care systems most. The resulting evidence will support decision makers in designing and tailoring policies to build patient-oriented, integrated health care and social services systems.

Preclinical development of a disease modifying small molecule therapy for Alzheimer disease

Dr. David Vocadlo is leading one of five BC researchers leading teams supported through the British Columbia Alzheimer’s Research Award. Established in 2013 by the Michael Smith Foundation for Health Research (MSFHR), Genome British Columbia (Genome BC), The Pacific Alzheimer Research Foundation (PARF) and Brain Canada, the goal of the $7.5 million fund is to discover the causes of and seek innovative treatments for Alzheimer’s disease and related dementias.

Alzheimer’s disease (AD) is a debilitating and progressive neurodegenerative disease, accounting for almost two-thirds of all dementias in Canada, and in BC affects up to 70,000 people. Symptoms include memory loss, behaviour and personality changes, and a decline in cognitive abilities.

Current AD medications treat symptoms of the disease, but none exist that can stop or even slow the progression of AD which starts in the brain many years before it manifests. The need for AD therapies that treat underlying progression of the disease is paramount for the aging population, in particular because of the projected increase in the number of AD patients.

Dr. David Vocadlo, a professor in Chemistry and Molecular Biology & Biochemistry and Canada Research Chair in Chemical Biology at Simon Fraser University (SFU), aims to address several key challenges that would clear the way for a promising new AD therapeutic target.

The two biological hallmarks of Alzheimer's disease in the brain, neurofibrillary tangles and amyloid plaques, are caused by the dysfunction and abnormal accumulation of specific proteins that can kill brain cells over time, progressively impairing brain function.

Vocadlo and a multidisciplinary group of research teams from SFU, the University of British Columbia (UBC) and the University of York in the UK, are pioneering their new approach that has been shown to block disease progression in animal models of AD by blocking the toxicity of the brain proteins that form the tangles within brains. Their approach centres on a specialized sugar unit called O-GlcNAc. Clumps of protein from AD brains have almost none of this sugar attached to them because the O-GlcNAcase enzyme continues to remove this sugar modification.

Vocadlo’s therapeutic goal is to use small molecules to block the activity of the O-GlcNAcase enzyme, and in this way increase the levels of O-GlcNAc in the brain to prevent this protein from clumping together and becoming toxic. Vocadlo’s team is currently advancing this therapeutic target in order to advance it into the clinic.

The impact of opioid agonist treatment on antipsychotic adherence among justice-involved patients in British Columbia

Substance dependence and mental illness frequently co-occur, presenting challenges to treatment providers and increasing the likelihood of suicide, drug overdose, and criminal justice involvement. Assessment and treatment of concurrent disorders (CD) have been identified by police, health professionals, and the Auditor General as urgent priorities in BC, and leadership in the treatment of CD is integral to the mandate of the Provincial Health Services Authority. 

Despite well-documented personal and public risks associated with schizophrenia and opioid dependence, little research has examined the combination of these disorders. Medications, including methadone and antipsychotic drugs, are the first line treatments for patients with these diagnoses. Recent studies, including research conducted in BC, have revealed low levels of adherence to these prescribed medications, leading to increased risks of violence, property crime, and mortality. 

Researchers investigating HIV/AIDS have shown that when opiate dependent patients are adherent to methadone they are also more likely to follow their HIV/AIDS treatment. This research will investigate whether methadone adherence similarly increases adherence to antipsychotic treatment and leads to superior outcomes for patients diagnosed with both disorders.