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).

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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).

Silent genomes: Reducing health care disparities and improving diagnostic success for children with genetic diseases from Indigenous populations

Health Research BC is providing match funds for this research project, which is funded by the Genome Canada/CIHR Large-Scale Applied Research Project (LSARP): Genomics and Precision Health funding opportunity. Additional support is provided by Genome BC, the BC Children’s Hospital Foundation, BC Provincial Services Health Authority and the University of British Columbia (UBC).

 

Indigenous populations in Canada and around the world face unique health challenges, inequities, and barriers to healthcare. As a result, they typically have poorer health outcomes than non-Indigenous groups.

 

The health disparity gap widens when it comes to Indigenous populations’ access to the technology and research involved in genomics – the study of the complete set of human genes – which have advanced health care by allowing medical treatments to be tailored to the specific needs of individual patients through precision medicine, routinely available to other Canadians.

 

Dr. Laura Arbour, a clinical geneticist at BC Children’s Hospital and Island Health, and a professor in UBC’s Department of Medical Genetics, is working to address the growing genomic divide – particularly the lack of background genetic variation data for Indigenous populations – through the Silent Genomes project. The four-year project aims to improve health outcomes by reducing health disparities, enhancing equitable access to diagnosis, treatment, and care for Indigenous children with genetic diseases. Arbour is joined on the project by the University of Northern British Columbia’s Dr. Nadine Caron, and Dr. Wyeth Wasserman from UBC and the BC Children’s Hospital Research Institute, where the research will be conducted, along with BC Women’s Hospital + Health Centre.

 

The Silent Genomes research team will work with First Nations, Inuit and Métis partners across Canada to establish processes for Indigenous-led governance of biological samples and genome data, leading to policy guidelines and best practice models for genomic research and clinical care.

 

The project will also create an Indigenous Background Variant Library (IBVL) of genetic variation from a pool of 1,500 First Nations Canadians that will improve the accuracy of genomic diagnosis by providing necessary reference data for Indigenous populations living in Canada and globally. Researchers will also assess the effectiveness of the IBVL to lower health care costs, and plan for long-term use of the IBVL for Canadian Indigenous children and adults needing genetic/genomic health care.


End of Award Update – July 2024

 

Results:

The Silent Genomes Project (SGP) successfully achieved four main objectives:

  1. Established Indigenous-informed policies for Indigenous governance over biological data through the S-GIRDD Steering Committee.
  2. Developed a comprehensive Background Variant Library (IBVL) using genomic data from First Nations participants, that was operational in January 2024, allowing internal testing with potential for expansion with more genomes from Indigenous participants.
  3. Conducted whole genome sequencing for Indigenous patients with suspected genetic diseases, with standard analysis completed for 89 patients/families and ongoing analysis for unresolved cases.
  4. Provided research training for Indigenous students in precision diagnosis and health economics over a six-year period. With the scholarship support of Life labs, the project team ensured the participation of over 30 students in the first 5 SING Canada workshops.

 

Impact:

  1. Governance within the Silent Genomes Project ensured development of policies and operational guidelines for Indigenous involvement in genomic research. The Silent Genomes Indigenous Rare Disease Diagnosis Steering Committee has developed the processes for variant release which were implemented for the IBVL, protocols for clinical research applications planning to use the IBVL, and review process for the manuscripts where IBVL was used for the variant selection. The process of transformation of the advisory S-GIRDD Steering Committee into the sustainable IBVL Governance Committee is underway. The project leadership and the S-GIRDD committee members participated in the 2nd “DNA on Loan” conference organized by CIHR, where gaps in currently existing guidelines, that the team was exposed through the SG lifetime, have been discussed. Internationally, utilizing the mechanism approved by the S-GIRDD (online restricted access to frequency of Indigenous variants) within accepted upon ethical frameworks (CARE principles), was reviewed and is under consideration by two other jurisdictions (Australia and New Zealand).
  2. Efforts were made to enhance the capacity of healthcare providers, Indigenous patients, communities, and students to engage with genomics research and health care. Five SING Canada workshops were conducted by Dr. Tall bear and her team, with the support of SG team members. Additionally, two Indigenous graduate students have either completed or are nearing completion of their studies. Educational materials developed by Activity 1 are available on the Silent Genomes website, along with regularly updated content on Genetics and Genomics research best practices.
  3. The first release of the Indigenous Background Variant Library (IBVL) is undergoing testing and will be available for clinical use within the next few months. Once completed, this effort will enable assessment of how genomic variant knowledge impacts diagnostic clarity for Indigenous patients with rare diseases. The SGIRDD Steering Committee is actively involved in developing sustainable IBVL usage processes beyond the project’s duration. Internationally, the pipeline and user interface developed within the project have been shared with the Varoomed Project (Aotearoa/New Zealand), for testing or partial adoption.
  4. Aims to increase access to genetically based diagnoses and care involved closing enrollment and engaging National Clinical Network (NCN) teams across 11 Canadian sites, with ongoing discussions to address limitations in Canadian TCPS2 Chapter 9 guidelines. Efforts were made to raise awareness among healthcare providers regarding barriers to accessing clinical and research genomics post-project. The Culturally Informed Genetic Counselling Guide, provided to each site, has been published on the SG Best Practices website for wider dissemination. The NCN continues to work on breaking down barriers to access to clinical and research genomics.

 

Potential Influence:

  1. The lessons learned while establishing a National Clinical Network will be used to break down barriers in access to clinical and research genomics for Indigenous peoples.
  2. Further collaborations are needed to fill the existing gaps in policies and guidelines related to Indigenous involvement in genomic research.
  3. The S-GIRDD Steering Committee is currently focused on developing processes for sustainable use of the IBVL beyond the Silent Genomes project, with the goal of independent continuous seamless governance and technical support during the lifetime of the IBVL.
  4. The international “Be FAIR and CARE” meeting gathered international Indigenous Genomics specialists from around the world, which conceived an idea of creating an International Indigenous Genomics Advisory and Research Consortium which would provide the necessary skills and knowledge for the development of stipulations for Indigenous data sharing processes globally. If similar projects are using comparable pipelines and user interface (e.g. the ones developed within the project), it may technically ease global data sharing processes.
  5. The Health Economics study developed a set of practical and collaborative approaches for qualitative research when working with Indigenous People and communities to provide opportunities to advance Indigenous governance, capacity, and equity approaches.

 

Next Steps:

Building upon the original SGP, the new extended work is intended to catalyze longer-term efforts that could be sustained under healthcare systems (as the reference data provided by the IBVL becomes standard of care for diagnostic testing), funded by grants such as an anticipated Genome Canada health competition, directly supported through federal allocation, or a mixture of these models. Over the next 5 years, there are four key foci. First, developing sustained funding for the IBVL as an integrated reference data source for clinical diagnosis of rare disease. Second, achieving broader inclusion of Indigenous communities in the IBVL to enable the reference data to be of equitable utility for all Indigenous peoples of Canada. Third, to build upon emerging capacity to substantially increase the number of Indigenous researchers, research leaders, and genetic/genomic health care providers. Fourth, to identify and develop new health-related applications requiring reference data that are of priority to Indigenous peoples.

Seniors Adding Life to Years (SALTY)

Health Research BC is providing match funds for this research project, which is funded by CIHR’s Team Operating Grant: Late Life Issues. Additional support is provided by Nova Scotia Health Research Foundation, Alberta Innovates Health Solutions and Alzheimer Society of Canada.

 

Late life is a time when older adults and their caregivers face health and social issues that can impact their well-being. Everyone wants to live well in their final years, but this may be a challenge, particularly for people living in residential long-term care (LTC) settings.

 

A multi-disciplinary, multi-sectoral team of researchers, care providers, administrators, policy makers and older adults and their families from across Canada have come together to better understand how to add quality to years in the last phase of life for people in residential care and their caregivers. Seniors-Adding Life To Years (SALTY) is a four-year research project that will evaluate promising programs, practices and policies currently employed in four provinces – British Columbia, Alberta, Ontario and Nova Scotia – to support change in how decision makers and practitioners provide care and support in long-term care across the country.

 

Led by professor Janice Keefe at Mount Saint Vincent University and director of the Nova Scotia Centre on Aging, the study team will develop innovative strategies to understand and assess the impact of existing programs on quality of care and quality of life, with the goal of rolling out effective approaches in jurisdictions across Canada.

 

SALTY’s research program is organized in four interrelated research streams or problem areas, each applying a different perspective to the late-life trajectory in LTC. Dr. Kelli Stajduhar, of the University of Victoria’s (UVIC) School of Nursing and Institute on Aging and Lifelong Health is co-leading one of the streams. Stajduhar is joined by Drs. Denise Cloutier, also with the Centre of aging and UVIC’s department of geography, and Leah MacDonald, medical director of Island Health’s End-of-Life program. The BC research team is evaluating an implementation project entitled “Improving End-of-Life Outcomes in Residential Care” taking place in four Vancouver Island LTC homes. The goal of the implementation project is to facilitate a promising palliative approach in the context of care provided in LTC facilities for people with life-limiting conditions. Additionally, the team’s evaluation will provide evidence to support application of the project in other provinces.

Locally produced brain insulin in memory and Alzheimer’s disease: A multi-disciplinary approach to a key question

Dr. James Johnson is 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) – the most common form of dementia – is a fatal, progressive and degenerative disease that destroys brain cells, causing thinking ability and memory to deteriorate.

 

One percent of AD is the early-onset type that runs in families. While extensive studies of these forms of the disease have revealed the genes that cause them, the most common, late-onset forms of AD are understudied and poorly understood at the level required for therapeutic intervention.

 

Studies have shown links between Alzheimer’s disease and obesity, altered fat metabolism, insulin and diabetes, with diabetes increasing the risk of suffering from AD by 30-65 percent. Scientists have also found the brain produces a small amount of insulin with reduced levels in the brains of AD sufferers. While the function of brain insulin is a mystery, evidence suggests reduced brain insulin could play a role in Alzheimer’s disease.

 

Dr. James Johnson, a professor in the Departments of Cellular and Physiological Sciences and Surgery at the University of British Columbia (UBC), further found in preliminary studies that high-fat diets reduced brain insulin production. The goal of Johnson’s continuing research is to answer the key question: is the loss of brain insulin alone enough to cause cognitive impairment? Johnson will test the hypothesis that brain-produced insulin is a critical factor for the survival and function of brain cells in the context of both a genetic change that increases Alzheimer’s risk and a diet that increases Alzheimer’s risk. Using mice models lacking brain insulin, Johnson’s team will assess their ability to learn and study how their brains are reprogrammed. Insulin will be correlated with Alzheimer’s-like changes in human brains.

 

Information on the role and mechanisms of brain insulin through Johnson’s pioneering research has the potential to advance understanding of AD and contribute to an eventual cure. Identifying the link between diet, insulin and Alzheimer’s disease could also enable earlier diagnosis and inform strategies for Alzheimer’s prevention. Furthermore, the findings may shed light on much-needed new drug targets for Alzheimer’s disease or possibly re-purposing existing diabetes drugs.

Diabetic retinopathy screening – National tele-ophthalmology

MSFHR is providing matching funds to support the research of Dr. David Maberley as part of Diabetes Action Canada, one of five national chronic disease networks established through the Canadian Institutes of Health Research’s (CIHR) Strategy for Patient-Oriented Research (SPOR) Networks in Chronic Disease, connecting researchers, health professionals, policy-makers, and patients across the country. MSFHR has committed funding over five years to support Diabetes Action Canada and the BC-based research activities of two other networks: Can-SOLVE CKD and CHILD-BRIGHT.

Diabetes is considered a global epidemic. By 2025, over 12 percent of the Canadian population will live with diabetes. Diabetes can damage the back of the eye (retina) causing swelling, bleeding and scarring which can lead to deterioration and loss of eyesight. Diabetic Retinopathy (DR) is a serious complication of diabetes and the leading cause of blindness in adults under 60 years of age. It is asymptomatic in the early stage, but can quickly progress to more advanced stages, and if left untreated, can lead to severe vision loss, and even blindness. Almost all people with Type-1 diabetes and more than 60 per cent of those with Type-2 develop some form of retinopathy in the first two decades after a diabetes diagnosis. In Canada, the rate of diabetic retinopathy is about 40 per cent higher in First Nations communities compared to the general population.

Early detection of DR, through regular screening of the retina, is an effective method of avoiding vision loss from diabetes. There are effective therapies that can prevent visual loss and slow the progression of the damage if detected early. Therefore, it is critical to screen all people living with diabetes for early or more advanced diabetic retinopathy.

Dr. David Maberley, head of the Department of Ophthalmology and Visual Sciences at the University of British Columbia (UBC), is co-leading a national retinopathy screening program for the early diagnosis and management of DR with Dr. Michael Brent from the University of Toronto. Maberley’s research is a component of Diabetes Action Canada – the first and only nation-wide collaborative network of clinicians, researchers, disease associations, industry and government in partnership with people living with diabetes – focused on the prevention of diabetes complications.

The focus of Maberley’s BC research is to evaluate a DR screening site in Vancouver’s Downtown East Side and in remote First Nation communities. These sites will provide a model for community-based screening to improve care for patients with diabetic retinopathy living in remote and under-served areas of BC. Diagnostic nodes will be established in several rural hospitals and equipped with optical coherence tomography (OCT) cameras using new software for automated retina image data capture, transfer and analysis to detect retinal degeneration before symptoms emerge. As well, two travelling screening cameras will serve remote communities. These advanced imaging procedures will allow for the segmentation of patients according to risk, for treatment and follow-up care. For patients, availability of DR screening closer to where they live means they only have to make trips to the larger centres when treatment is actually needed.

Maberley’s team will also explore the use of artificial intelligence (AI) to allow images from OCT cameras across the country to be analyzed instantly to determine the need for treatment at an advanced centre, and inform clinicians on the course of treatment. Another component is the development of an app to assist patients with managing their eye care.

New advancements in imaging technology will enhance the ability to identify the full spectrum of diabetes-related retinal disease and allow for detection and intervention at earlier stages in the disease process. Maberley’s research will support Diabetes Action Canada’s goal to develop a national DR assessment program and patient registry to facilitate clinical trials of new diagnostic methods and more effective treatments, accessible to all Canadians with diabetes, ultimately transforming health outcomes, with few people losing their vision as a result of their diabetes.

CHILD-BRIGHT: Child Health Initiatives Limiting Disability – Brain Research Improving Growth and Health Trajectories

Health Research BC is providing match funds for this research project, which is funded by the Canadian Institutes of Health Research’s (CIHR) Strategy for Patient-Oriented Research (SPOR) Networks in Chronic Disease

 

As many as 850,000 children in Canada are living with a brain-based developmental disability (BDD). They face lifelong challenges with mobility, language, learning, socialization and self-care, which impacts their quality of life and create special challenges for their families. They also typically have poorer health, lower educational achievement, fewer economic opportunities and higher rates of poverty than children without disabilities.

 

CHILD-BRIGHT is a pan-Canadian network of clinicians, patients, families and scientists committed to making the future brighter for infants, children and youth with lifelong brain-based developmental disabilities and their families. The five-year project focuses on those diagnosed with a brain-based disorder such as autism, cerebral palsy, fetal alcohol spectrum disorder, learning or intellectual disabilities, as well as those at high risk for a brain-based developmental disability due to pre-term delivery, congenital heart disease, or genetic anomalies.

 

Dr. Dan Goldowitz, a professor of Medical Genetics at UBC and the Centre for Molecular Medicine and Therapeutics at the BC Children’s Hospital Research Institute, is one of CHILD-BRIGHT’s three co-directors, along with Drs. Steven Miller at University of Toronto/The Hospital for Sick Children (SickKids), and Network Director Annette Majnemer of McGill University Health Centre’s Research Institute.

 

CHILD-BRIGHT’S 12 patient-oriented research projects fall under three themes: “Bright Beginnings” – innovative early therapies to optimize brain and developmental outcomes; “Bright Supports” – integrating mental health and wellness support into care for children and youth, and “Bright Futures” – re-designing key parts of health care services to be more responsive to family needs, throughout the trajectory of the child’s and the family’s development.

 

Goldowitz is overseeing the network’s training program. His UBC team will engage with patients, researchers and policy-makers to foster a culture of patient-oriented research that could help serve as a model for future health research and lead to better outcomes for patients and their families.

 


 

End of Award Update: May 2022

 

Results

Training Program – CHILD-BRIGHT’s Training Program has worked to develop capacity in patient-oriented research (POR) to ensure that authentic patient-partner engagement is fundamental to the research process. To this end, regular training offerings such as webinars, workshops, and self-directed modules, have been critical. However, initiatives that strive towards changing the research culture around POR will have a far lasting impact. For instance, the Summer Studentship Training Program exposes undergraduate students to the core tenets of POR while providing opportunities to gain practical experience within a CHILDBRIGHT research project. Funding initiatives such as the “Graduate Student Fellowship in POR” provides support to graduate trainees or postdoctoral fellows to augment a research project to involve the patient-partner voice. Together, outputs like this help create capacity for POR in tomorrow’s research leaders.

 

Parent-EPIQ – In the Parent-EPIQ studies, we found that we need to revise how we talk about the futures of children born very preterm. Parents want a broader perspective with positive and negative outcomes including functioning, quality of life and family wellbeing. We also successfully implemented interventions to improve language abilities in children born preterm using the proven EPIQ quality improvement technique with parent involvement. Lastly, we provided up to date Canadian information for parents and health care providers in four annual reports.

 

IMAGINE – This project has determined that approximately half of children affected with symptoms of atypical cerebral palsy can be provided with a genetic diagnosis when trio whole genome sequencing is used. We also determined that trio whole genome sequencing is superior in diagnostic power to the currently used clinical exome sequencing. Bioinformatics pipelines were created to optimize diagnoses via these whole genome methods. These have been presented and published or are in press. Several patient-facing tools were developed for this project, in conjunction with parent-partners associated with the project. All were well accepted and appreciated, which supports the advantages of parent partner involvement.

 

PIUO – Many infants, children and youth with rare diseases and complex conditions affecting the central nervous system often experience pain and irritability. Sometimes the pain is due to medical procedures such as scoliosis repairs, or due to chronic conditions such as muscle spasms. There are, however, many times when it is difficult to find a source as these children often have severe language delays. Engaging clinicians in assessing and treating PIUO using history, physical examinations, diagnostic tests, and screens to rule out unknown causes of indeterminate pain has influenced the way this issue is being treated clinically. The pathway also provides support and guidance for parents of these children.

 

 

 

 

Impact

Parent-EPIQ – As a result of the Parent-EPIQ project, our work has highlighted what parents view as important: functioning, quality of life and family well-being. These areas are not currently captured in data collection as part of the Canadian Neonatal Follow Up Network. This major impact of work has been taking steps to shift the paradigm of reported outcomes in neonatal follow up research using these findings through changes to our annual report and data collection, implementing recommendations from parents of preterm children, and considering parent perspectives when reviewing and evaluating data requests and future research.

 

IMAGINE – The results of this project have provided a diagnosis to families who previously had no etiology for their child or children’s problems. This has provided an explanation for these families, and in many cases genetic counseling has provided information on the trajectory of the illness, risk to other family members and to future pregnancies. An understanding of etiology enables treatment options to be considered. One of the patient-facing tools, the Genomic Results Booklet, has been tested in clinical usage in the BC Children’s Hospital Pediatric Neurology. This clinic has seen the importance and advantages of providing post-testing information in this format. A research paper is currently under development that describes the impact of this tool in clinical use.

 

PIUO – Many infants, children and youth with rare diseases and complex conditions affecting the central nervous system often experience pain and irritability. Sometimes the pain is due to medical procedures such as scoliosis repairs, or due to chronic conditions such as muscle spasms. There are, however, many times when it is difficult to find a source as these children often have severe language delays. Engaging clinicians in assessing and treating PIUO using history, physical examinations, diagnostic tests and screens to rule out unknown causes of indeterminate pain has influenced the way this issue is being treated clinically. The pathway also provides support and guidance for parents of these children.

 

 

Potential Influence

Parent-EPIQ – We have leveraged powerful partnerships with parents and collaborations with advocacy groups to co-create resources and materials that directly reach families. Not only have we been able to disseminate our research findings through traditional academic publications, but we have pursued innovative and novel avenues to benefit more families and more children born preterm which is the ultimate objective of our work. Our research is being noticed. PI Dr. Synnes was invited to present results in Seoul, Korea and virtually to Boston Children’s Hospital in the fall of 2023.

 

IMAGINE – This project has provided evidence for the efficacy of the diagnostic and clinical care used: (1) approach of whole genome sequencing (2) bioinformatics pipeline, and (3) has demonstrated the advantages of parent involvement throughout. We hope that the presentations and academic papers produced will provide a framework for best practices for similar families.

 

PIUO – Our co-investigators were invited to speak in Prince George’s Northern University Hospital, and locally in several outreach clinics and hospital rounds about our pain pathway protocol. Our wider impact via the academic literature remains to be determined as we await statistical analysis for write up in research journals.

 

 

Next Steps

Parent-EPIQ – In this work, we have identified specific assessment tools to measure parent-identified outcomes. Future research will involve the feasibility of implementing these tools into routine data collection as part of the Canadian Neonatal Follow Up Network. The next steps will include leveraging the success of the CHILD-BRIGHT Phase 1 Parent-EPIQ project to start work on the CHILD-BRIGHT Phase 2 project: “Implementing Patient-Reported Outcome Measures (PROMs) in follow-up care of preterm children using a hybrid implementation-effectiveness design”.

 

IMAGINE – Our next steps include efforts towards knowledge mobilization and implementation science to identify how best to integrate what we have learned in this study into clinical practice. Future research will continue to finesse bioinformatics methods and re-examination of as-yet undiagnosed children. We are working on challenging variants that include complex sequence repeats and rearrangements.

 

PIUO – Our next steps will be to complete data analysis and use the results to inform an implementation science project as part of CHILD-BRIGHT Phase 2, which will allow our team to expand the pain pathway to pediatricians across BC.

Validation of connexins and pannexins as a target for Alzheimer’s disease

Dr. Christian Naus is 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 the most common form of dementia, accounting for almost two thirds of total cases. There are currently no successful treatments, making the discovery of effective therapeutic interventions critical.

 

The brain contains billions of neurons (nerve cells), and substantially more non-neuronal cells called glia. Astrocytes, the most abundant type of glial cells, closely interact with neurons to control the transmission of electrical impulses within the brain. The major disease hallmark of AD is cognitive decline linked to neuronal wasting, impairment and finally, death.

 

Dr. Christian Naus, a professor in the Department of Cellular and Physiological Sciences at the University of British Columbia (UBC) and Canada Research Chair in Gap Junctions and Neurological Disease, studies the molecular and cellular mechanisms by which astrocytes lose their ability to support neurons that are vulnerable to destruction in Alzheimer’s disease, with the aim to identify new drugs to aid in treatment.

 

Naus’ team examines a unique set of cellular channels in astrocytes and neurons formed by special proteins, called connexins and pannexins. These channels help control the environment in which the cells of the brain must function by allowing a variety of small molecules to pass freely from one cell to another, and allowing them to coordinate cellular responses to various signals. However, when these channels stop working properly, they can become damaging to the environment thus compromising the normal functions of neurons. Naus’ research explores the role of these channels in neurons and astrocytes in order to identify how to manipulate these channels to provide protection for neurons in cases of disease, such as AD.

 

The outcome of these studies will contribute to the potential identification and development of new drugs that will not only target neurons, but also enhance the ability of astrocytes to protect neurons that are vulnerable to cell death in AD.