Propagated protein misfolding of SOD1 in ALS: Exemplar for neurodegeneration

MSFHR supported Dr. Neil Cashman’s award as one of two interprovincial teams from across Canada funded through Brain Canada’s Multi-Investigator Research Initiative (MIRI) in 2013. The MIRI supports the research of multidisciplinary teams and aims to accelerate novel and transformative research that will fundamentally change the understanding of nervous system function and dysfunction and its impact on health. MSFHR committed funding over three years to support the work of Cashman’s BC-based research activities and research led by fellow MIRI recipient Dr. Terrance Snutch on the role of brain calcium channels in brain disorders. Additional support was provided by Genome BC, the University of British Columbia (UBC)/Vancouver Coastal Health and two Quebec-based research institutes.

Amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig’s disease, is a progressive fatal disease that affects the nerve cells responsible for muscle movement (motor neurons). ALS is characterized by the systematic paralysis of muscles due to the progressive death of motor neurons. An estimated 2,500 to 3,000 Canadians suffer from the disease, for which there is no cure or effective treatment. Each day, two to three people are lost to ALS, with 80 percent of affected individuals dying within two to five years of diagnosis. 

A study led by clinical neurologist and neuroscientist Dr. Neil Cashman at UBC has revealed how factors that cause ALS can be transmitted from cell to cell throughout the nervous system and suggests the spread of the disease could be blocked, pointing to new therapeutic approaches.

Neurodegenerative diseases like ALS belong to a larger group of illnesses known as protein misfolding diseases. Cashman, who holds the UBC Canada Research Chair in Neurodegeneration and Protein Misfolding, built on his hypothesis that certain proteins implicated in ALS, when abnormally shaped or misfolded, are prone to accumulate and cause motor neuron death. This disease mechanism has also been found in other neurological diseases, such as Alzheimer’s and Parkinson diseases. 

Cashman’s team used therapeutic antibodies that target and block these misfolded proteins to better understand the protein misfolding process and how the disease is transmitted throughout the nervous system. Cashman’s work can lead to identifying the best ways to stop the progressive neurological damage seen in ALS through the development of targeted treatments.

Integrating paramedics into primary care to optimize patient time in the community at end of life

Health Research BC is providing match funds for this research project, which is funded by CIHR’s Strategy for Patient Oriented Research (SPOR) Primary and Integrated Health Care Innovations (PIHCI) Network – Comparative Program and Policy Analysis Grant.

 

Many Canadians wish to spend their dying days at home. Despite this, 70 percent of deaths occur in hospital, the majority after a visit to the emergency department (ED). Paramedics, also known as emergency medical services (EMS), facilitate more than half of ED visits for patients receiving palliative care for a chronic condition.

 

One of the goals of British Columbia’s provincial palliative care strategies is to help enable people to stay at home as long as possible during their end of life. Currently, BC does not have a palliative care program within its Emergency Health Services (EHS).

 

Drs. Sabrina Wong and Jennifer Kryworuchko, faculty in the School of Nursing and Centre for Health Services and Policy Research at the University of British Columbia (UBC) are leading a team of researchers investigating innovative ways to deliver integrated emergency health services that support palliative care. The BC team collaborate with counterpart research team members in Nova Scotia who are examining the impact of the Nova Scotia EHS Special Patient Program on provincially funded health services and the ability to enable palliative patients to stay at home. Researchers will compare administrative health data from the two provinces on patients who received EHS paramedic services and died non-suddenly from chronic disease.

 

Since 2015, paramedics in Nova Scotia have received specialized clinical training on pain and symptom management and other care and support services for palliative patients as part of the Paramedics Providing Palliative Care at Home Project (PPPCHP). The PPPCHP is intended to enhance existing palliative care resources and the end-of-life experience for patients and their families/caregivers by bridging palliative care until their usual care team can take over. Researchers will identify the core elements of the PPPCHP essential for the program to be modified for rollout in BC.

 

In addition to improving end-of-life care and strengthening community-based care, the adoption of the Nova Scotia model in BC and other jurisdictions has the potential to reduce transport to the ED and avoid or reduce unwanted medical treatments, interventions and hospitalizations, contributing to reduced health care system costs.

Validation of administrative and primary care electronic medical record derived frailty algorithms

Health Research BC is providing match funds for this research project, which is funded by CIHR’s Strategy for Patient-Oriented Research (SPOR) Network in Primary and Integrated Health Care Innovation (PIHCI) – Quick Strikes initiative.

 

Frailty is a significant and growing issue in Canada. By 2025, two million Canadians will be living with frailty and 3.75 million Canadians will be caregivers. Characterized by reduced strength, endurance and physiological function, those who are frail or at risk of becoming increasingly frail are less resilient to recover from significant life events and respond to acute care treatments, and are vulnerable to further decline, dependence and death.

 

Dr. Sabrina Wong of the University of British Columbia’s School of Nursing and Centre for Health Services and Policy Research worked with Dr. Tyler Williamson from the University of Calgary and Dr. Alan Katz from the University of Manitoba on the development of tools to aid in the early detection and accurate identification of frailty in seniors, to supporting healthy aging and the needs of older adults.

 

Using data from seniors 65 years of age and older in British Columbia, Alberta, and Manitoba, they developed an algorithm for use with administrative health data and another for use with electronic medical record data. Researchers also engaged primary care clinicians and patients in developing ways to identify frailty and to detect the range of frailty in patients to be used as part of the algorithms.

 

Finally, they sought to implement the electronic medical record algorithm in the Canadian Primary Care Sentinel Surveillance Network’s (CPCSSN) web-based reporting tool, InQUIRE (Interactive Quality Improvement Reporting Environment) to provide timely feedback on frailty back to primary care clinicians.

 

The results of Wong’s study will provide new knowledge that could inform both clinical care and jurisdictional level health services planning across Canada in order to improve patient care, patients’ and caregivers’ quality of life and better use of the healthcare 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

Health Research BC is providing match funds for this research project, which is funded by CIHR’s Strategy for Patient Oriented Research (SPOR) Primary and Integrated Health Care Innovations (PIHCI) Network – Comparative Program and Policy Analysis Grant. Additional support is provided by 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.

Implementation and evaluation of an enhanced PharmaNet-based adverse drug event reporting platform to improve patient safety and meet adverse drug reaction reporting requirements

Health Research BC is providing match funds for this research project, which is funded by CIHR’s eHealth Innovation Partnership Program (eHIPP).

 

Each year in British Columbia, adverse drug events (ADEs), the unintended harmful reactions to medication use, result in 240,000 emergency department visits and 480,000 hospital days, with their treatment adding $90 million to health care costs. Seniors, the highest users of medications, experience the greatest proportion of adverse drug events.

 

Up to 70 percent of ADEs have been identified as preventable, with 30 percent occurring when health care providers unknowingly re-prescribe and re-dispense drugs that had previously harmed patients. Current electronic systems are not effective in preventing the unintentional prescribing of culprit or contraindicated drugs as ADEs are often not documented in medical records, and not communicated between care providers and across health care sectors.

 

Dr. Ellen Balka, a communication and technology expert and professor at Simon Fraser University (SFU) and Dr. Corinne Hohl from the University of British Columbia’s (UBC) Department of Emergency Medicine and Vancouver General Hospital are leading the ActionADE project to reduce ADEs. The team will implement and evaluate an ADE reporting platform through PharmaNet — BC’s provincial drug billing system — and integrate into existing health care practices. The goal of the platform is to bridge current information gaps and address the need for improved communication of ADEs across health care settings and providers by generating real-time patient- and medication-specific alerts about previous ADEs for clinicians when prescribing or dispensing medications.

 

The project team, based at the Vancouver Coastal Health Research Institute’s Centre for Epidemiology and Evaluation, worked with industry partner PHEMI of Vancouver to develop the ActionADE software that will be used by hospital-based and family physicians, in-hospital and community-based pharmacists and other health care providers. Decision-making authorities, including government and researchers, will have access to the data generated. It is estimated the ActionADE platform will help avoid as many as one-third of the preventable ADEs, translating into more than 40,000 fewer ED visits, saving the provincial health care system as much as $18 million annually.

 

In 2018, Hohl received an MSFHR Health Professional-Investigator Award related to this project.

Brain channelopathies – Target validation and novel therapeutic strategies

MSFHR supported Dr. Terry Snutch’s award as one of five interprovincial teams from across Canada funded through Brain Canada’s Multi-Investigator Research Initiative (MIRI). The MIRI supports the research of multidisciplinary teams and aims to accelerate novel and transformative research that will fundamentally change the understanding of nervous system function and dysfunction and its impact on health. MSFHR committed funding over three years to support the work of Snutch’s BC-based research activities and research led by fellow MIRI recipient Dr. Neil Cashman on the role of protein misfolding in Amyotrophic Lateral Sclerosis (ALS).

Continue reading “Brain channelopathies – Target validation and novel therapeutic strategies”

Deliberative public engagement to inform cancer control decision-making in Canada

Health Research BC is providing match funds for this research project, which is funded by CIHR’s Institute of Cancer Control (CIHR-ICR) Partnerships for Health Systems Improvement (PHSI) program. Additional support is provided by the Canadian Centre for Applied Research in Cancer Control and Canadian Association of Provincial Cancer Agencies.

 

Provincial and territorial governments face considerable challenges in making fair and sustainable health care funding decisions. These challenges are particularly evident in cancer control and care where expenditure has risen significantly in recent years compared to other areas of health care. Priority setting is the focus of health economics—a branch of economics concerned with issues related to the scarcity of healthcare resources. With cancer expected to continue to be the primary cause of death in Canada and anticipated to increase due to population growth and an aging population, priority setting is imperative.

 

Public input can assist policy-makers in developing policies that are fair, reflect citizens’ values, and are socially acceptable. Dr. Stuart Peacock, who holds the Leslie Diamond Chair in Cancer Survivorship, Faculty of Health Sciences at Simon Fraser University (SFU), is co-leading a four-year study on the use of deliberative public engagement to inform cancer control priority setting and decision-making in Canada.

 

The study is based at the Canadian Centre for Applied Research in Cancer Control (ARCC) where Peacock is a co-director and hosted by the BC Cancer Agency (BCCA). Peacock is joined by co-principal investigators Dr. Michael Burgess, from the W. Maurice Young Centre for Applied Ethics, School of Population and Public Health at the University of British Columbia (UBC) and Michael Sherar, CEO of Cancer Control Ontario.

 

The research team will develop, refine and expand methods of deliberative public engagement, with outputs from the study including: an “atlas” of priority setting processes in cancer control, a framework for deliberative public engagement, recommendations from deliberative public engagement at events relating to interventions and programs from across the cancer control continuum, development of tools and strategies, and recommendations for the most appropriate models of participatory governance.

 

Peacock’s study will result in values-based evidence that decision-makers at the national, provincial and territorial level can use to inform priority setting decisions for identifying effective and cost-efficient ways to improve cancer patient outcomes.

Delivery of self-management through a peer-support telehealth intervention in patients with cardiovascular disease: The Healing Circles Project

Health Research BC is providing match funds for this research project, which is funded by CIHR’s eHealth Innovation Partnership Program (eHIPP).

 

Cardiovascular disease (CVD) is a leading cause of death and disability in Canada, resulting in an estimated $22.2 billion in health care costs and lost productivity annually. Older adults are afflicted more than any other population, with many dealing with complex chronic conditions in isolation.

 

Patient self-management has been found to play a key role in improving patient health and reducing hospital admissions. Correspondingly, social and peer support, and timely access to credible information on managing CVD, are essential for patient self-management and quality of life. Over a four-year period, Dr. Scott Lear, a professor in the Faculty of Health Sciences and the Department of Biomedical Physiology and Kinesiology at Simon Fraser University, and his team based at St. Paul’s Hospital, will study the use of a new application, Healing Circles, that offers support to seniors with CVD while staying in their homes and communities.

 

Healing Circles is a private and secure peer support and self-management platform created through a partnership between university-based researchers, industry, decision-makers, clinicians and patients. The Healing Circles application, accessible on smartphones, tablets, and desktop or laptop computers, was developed by Curatio, a digital mobile health company, headquartered in Vancouver. Expansion of the use of Healing Circles by seniors with CVD builds on Lear’s pilot study of the application involving women with heart disease from across Canada. After ten weeks, the women reported being better able to manage their health through the peer support and knowledge gained.

 

Healing Circles Project participants form virtual ‘Circles’ with 8 to 10 other patients to connect with and support one another as they learn to live day-to-day with their CVD. Additionally, the 250 study participants can interact with all members of the wider Healing Circles community to share experiences. Investigators anticipate that CVD patients using the Healing Circles platform in their homes will have improved self-management skills compared to patients receiving usual care, and improved quality of life, preventing secondary complications and reducing the need for health care and hospital use.

CCNA Team 13: Frontotemporal dementia

Dr. Robin Hsiung’s research is part of the Canadian Consortium for Neurodegeneration in Aging (CCNA) initiative funded by a national partnership between the Canadian Institutes of Health Research (CIHR) and 14 organizations from the public and private sectors across Canada, including MSFHR. The CCNA was created in 2014, bringing together more than 350 clinicians and researchers from across Canada. Organized into 20 teams based on their area of specialized expertise, researchers will focus on preventing and delaying the onset of dementia, as well as improving the quality of life for the estimated 560,000 Canadians affected. MSFHR is also supporting the research of two other BC-based researchers leading CCNA teams: Dr. Neil. Cashman (protein misfolding) and Dr. Cheryl Wellington (lipid and lipoprotein metabolism).

Frontotemporal dementia (FTD) is a progressive neurodegenerative syndrome, and the second most common cause of young-onset dementia after Alzheimer’s disease. FTD is an umbrella term for a diverse group of disorders characterized by the gradual wasting away of the brain’s frontal and anterior temporal lobes, progressively affecting mental function, personality and behaviour, while leaving memory largely intact.

Dr. Ging-Yuek Robin Hsiung, an associate professor in the Department of Medicine (Division of Neurology) at the University of British Columbia (UBC), and staff neurologist at the UBC Hospital Clinic for Alzheimer and Related Disorders, is leading the CCNA Frontotemporal Dementia (FTD) Team.

The team of more than 15 researchers from 8 institutions across Canada will examine the factors that cause FTD and explore new laboratory and imaging techniques to help identify and distinguish the various types of dementia. The goal of the FTD team includes establishing a registry of FTD subjects from across Canada that will contribute genetic and epidemiological information and organized into a national repository of samples. The data will provide important insights into related neurodegenerative disorders such as Alzheimer’s disease and amyotrophic lateral sclerosis (ALS), as well as other more uncommon brain disorders including ancorticobasal degeneration (CBD) and progressive supranuclear palsy (PSP).