Award Recipients: 2024 Transformation

Challenge:

Despite advanced therapeutic strides, the management and treatment of a wide range of diseases, from chronic conditions like cardiovascular diseases, osteoarthritis, and neuropsychiatric disorders to acute conditions like ischemia-reperfusion injury, are hindered by a common cellular antagonist: mitochondrial dysfunction. This dysfunction in our cells' powerhouses obstructs disease remission, leads to organ damage, and increases the risk of organ failure. Existing treatments are unable to effectively reverse or mitigate mitochondrial dysfunction, posing significant hurdles for disease management and treatment.

Innovation:

Our project, "Mitochondrial Transplant: Powering the Revolution in Regenerative Medicine," seeks to revolutionize medicine by harnessing the transformative potential of mitochondrial transplant to redefine disease treatment and mitigate chronic healthcare burden. Mitochondrial transplant involves the integration of healthy and viable mitochondria into injured cells or organs, potentially reversing organ damage and averting failures. The project is pioneering not only in its approach to treat mitochondrial dysfunction across a spectrum of diseases, but to fundamentally reshape organ regeneration and transplant outcomes. By focusing on the synergy between the precise delivery of functionally intact mitochondria and mitochondrial haplogroup matching we will amplify organ regeneration, disease treatment and transplant outcomes.

Goal: Uniting experts from biological, clinical, AI, statistical, legal, and materials engineering, we foster groundbreaking interdisciplinary research. The team has prior record of agility to adapt and implement findings in a clinical setting, making our work both translationally relevant and attainable. Utilizing innovative organ-on-a-chip, small and large animal models, we will simulate and evaluate the therapeutic implications of mitochondrial transplant at micro-and macro-scales, including feasibility, safety, and efficacy. We will additionally develop scalable storage and delivery systems and employ AI-driven engineering for maximum effectiveness. Ultimately, the outcome of this proposal is to conduct clinical trials to demonstrate safety, feasibility, and efficacy of mitochondrial transplant to transform medical practice.

Impact:

The impact of our project is substantial and far-reaching, including:

1) reversing organ degeneration:

We have the potential to significantly boost the body's ability to regenerate damaged organs to an extent that current therapeutic options simply cannot, since they rely on an already compromised cell machinery to overcome its established mitochondrial dysfunction.

2) Improving disease outcomes:

This approach can lead to better outcomes in both acute and chronic inflammatory diseases with important socioeconomic implications, considering the generalizability of the concept of mitochondrial transplantation, the relatively low costs associated with mitochondrial isolation techniques, and the potentially profound impact on organ function.

3) Increasing success rates in organ transplantation:

By extending the functionality of transplanted organs, we can increase the donor pool and reduce waitlist times. Our project, with its innovative and interdisciplinary approach, is poised to be at the forefront of mitochondrial regenerative medicine by addressing a critical challenge in healthcare reshaping how we treat diseases and improve patient outcomes.

Our team's interdisciplinary synergy unites diverse methods to approach mitochondrial transplant from foundational research to clinical application:

Therapeutic Efficacy approach: Verifying the therapeutic efficacy and safety of mitochondrial transplantation across multiple disease models and organs. Through human-derived organ-on-a-chip models, like cardiac, lung, liver, joint, and cerebral, and small and large animal studies, we'll evaluate the therapeutic implications of mitochondrial transplant in a controlled environment, ensuring its safety and reliability in humans.

AI-driven scalability approach: Designing and establishing scalable mitochondrial storage and delivery systems while leveraging AI-driven coating design and materials engineering. Our goal is to craft specialized solutions that are optimized for mass production and clinical relevance. Concurrently, using both AI and domain expertise, we'll work on enhancing mitochondrial transplant viability and efficacy by validating polymeric coating materials. Additionally, we'll incorporate insights from indigenous medicine, exploring how certain materials and chemicals utilized traditionally might be synthesized or used in tandem with mitochondrial transplantation as excipients or supplementary treatments.

Investigational approach: Focusing on the role of mitochondrial haplogroup matching, akin to HLA matching but at the mitochondrial level, in optimizing the efficacy of mitochondrial transplants. Through this alignment, we aim to enhance the outcomes of mitochondrial transplantation for management and treatment of a range of diseases and improve the success rates in organ transplantation.

Clinical approach: Conducting clinical trials to gauge the real-world effectiveness and safety of mitochondrial transplant. We will be testing whether mitochondrial transplant and haplogroup matching can become a medical standard, enhancing disease outcomes and patient’s quality of life.

The potential changes stemming from our research program are profound:

1) Powering Organ Regeneration: We envision a future where damaged organs can be revitalized and regenerated, offering hope and improved quality of life for patients facing organ failure.

2) Enhanced Disease Outcomes: By tackling the root cause of mitochondrial dysfunction, we aim to shift the paradigm of disease treatment. This could result in significantly improved outcomes for individuals grappling with both acute and chronic inflammatory diseases.

3) Enhanced Therapeutic Efficiency: Leveraging the combined expertise of AI-driven designs, materials engineering, and indigenous medicine insights, we can potentially create optimized mitochondrial transplant systems.

4)Revolutionized Organ Transplant: Through our work, we aspire to elevate the success rate of transplantation by extending the viability of transplanted organs and generating longer timeframes for planned surgical procedures, allow time for organs to be subjected to novel complementary therapeutic interventions, and potentially increase the reach of the organ pool to patients who would otherwise lack the opportunity for a life-changing procedure. Our program exemplifies collaboration-driven innovation. With support from the Mitochondrial Innovation Initiative and our strategic partners, we're well-equipped to establish mitochondrial transplant as a clinical standard, marking a new age in regenerative medicine and positively impacting patients globally.

Paralysis is a devastating neurological condition with no current cure. It can result from many causes, including stroke, multiple sclerosis, spinal cord injury, and traumatic brain injury. In most cases, the deficit is irreversible and strongly impacts quality of life. Yet, seemingly paralyzed muscles often retain some level of function because the neuronal circuitry controlling them – mainly located in the spinal cord – is largely intact. It is therefore possible to control a paralyzed limb with a neuromodulation system that detects a person’s intention to move, bypasses the lesion, and transmits commands to the affected muscles.

Various proof-of-concept studies have demonstrated the feasibility of neuromodulation for movement recovery, including restoring foot dorsiflexion after stroke and leg movement after thoracic SCI. Although these studies have led to the development of human-machine interfaces that can modulate the brain, spinal cord, peripheral nerves, and muscles with the outmost precision, only a minority of individuals living with paralysis have a disability that can be addressed by current systems.

This is due to four outstanding issues:
1) Interoperability: Current neuromodulation systems are mainly proprietary and embedded with vendor-specific components that are vertically integrated. While providing reliability and facilitating regulatory approval, these closed components prevent the integration of newer technologies that researchers and clinicians could use to meet the needs of individuals living with paralysis. This negatively impacts the accessibility and affordability of existing products, the social acceptability of upcoming devices using advanced data processing and sharing features, and the creation of new solutions by startups or academia.

2) Customization: Because paralysis can affect any combination of muscles through lesions in many different parts of the nervous system, the movements and circuits needing restoration vary widely across conditions and individuals. Consequently, neuromodulation systems must be customizable. To be scalable, such customization cannot involve new hardware or software developments for each specific use.

3) Somatosensation: To produce functional movements, simply generating muscle contractions is insufficient. People need to “feel” their movements to control them. Somatosensation is interrupted in many cases of paralysis and must be restored for movements to look and feel natural.

4) Translation: Results from animal models do not always perfectly translate to humans. Some functions, such as somatosensation and postural control when sitting, standing or walking are particularly challenging to test in animals and are at higher risk of translational failure. To successfully restore these functions in humans, multiple cycles of technological development, animal testing and human validation will be required. Streamlining and accelerating the translational process is critical and requires collaboration between basic neuroscientists, clinicians, regulatory experts, ethicists and engineers so that proof-of-principle animal experiments address the specificities of later human trials. The overall goal of project RE-MOVE is to enable the natural control of paralyzed muscles using a novel and flexible neuromodulation approach incorporating real-time user control and somatosensory feedback. We will provide paralyzed individuals with a choice of controllers (e.g., cortical sensor, haptic glove, EMG sensors) that they will be trained to use to control functionally relevant movements (e.g., foot dorsiflexion, hip flexion, knee flexion) triggered by real-time stimulation of an appropriate structure (e.g., spinal cord, peripheral nerve, muscle). Somatosensory data (e.g., joint position sense, touch, vibration, temperature, pain) will be collected and delivered back to the user to update the motor command in real-time. We will thus establish a library of stimulation paradigms, commercially available sensor technologies, and control algorithms that will be integrated in a core, free, expandable, and open software platform named NEO. The system will be built using an ethics-by-design approach that will proactively and continuously monitor arising ethical issues and incorporate technical, governance and regulatory solutions within the platform itself as it is being developed.

The project will be structured around three Objectives:

Objective 1: Assess the multifaceted needs and preferences of people living with paralysis and establish ethical and regulatory frameworks that will guide the development and implementation of NEO.

Objective 2: Test and develop neuromodulation strategies to generate specific movements with somatosensory feedback in animal models.

Objective 3: Translate the neuromodulation strategies of Objective 2 to people living with paralysis through an adaptive human feasibility study. Each Objective will be accomplished through a combination of focus groups, animal experiments (in cat and non-human primate models), technological developments, ethical workshops, and regulatory review. They will culminate in the conduct of a human feasibility study demonstrating movement restoration in 12 participants with stroke, multiple sclerosis, or spinal cord injury. Our ambition is that the NEO software will be so intuitive, powerful, accessible, and safe that it will become the de facto standard used by laboratories worldwide. By providing a robust infrastructure on which any neuromodulation experiments can easily be ran, we will spare researchers the need to constantly develop redundant software and allow them to instead focus on science. The software will be an expandable “plug-and-play” environment where only the components specific to the experiment will need to be developed using plugins that can be easily shared with the scientific community. This will empower people to explore new ideas in all fields of medicine, fundamentally transforming how neuroscience research is conducted and making neuromodulation accessible to all teams.

The project should provide transformative changes at multiple levels, including: 1) individuals living with paralysis (movement restoration, increased independence, improved quality of life); 2) health care systems (switch from community-based adaptation of the living environment to hospital-based restorative surgery); 3) research community (lowering the barriers to initiate neuromodulation research); 4) industry (facilitate technology transfers and accelerate commercialization of new ideas); 5) society (keep neuromodulation open and public, while stimulating ethical debates, producing innovations in governance, and improving regulations).

There is no place on Earth that will avoid the impacts of climate change. Carbon dioxide (CO2) emissions are over 50% higher than 40 years ago, when scientists’ warnings began to inform political discourse. The impacts are causing long-lasting changes to the climate system and likely to result in irreversible consequences if we do not act now. Global economic losses are exponentially increasing from climate-related disasters, which currently are in the trillions of dollars annually. For Earth to sustain human life, there must be rapid and aggressive reductions in carbon emissions from both elimination of emissions and large scale removal of CO2 from the atmosphere. Solid Carbon’s goal is the latter where the research need is great and urgent. The consensus now is that CO2 removal (CDR) strategies will be needed as early as 2038 to sustain human life and rich biodiversity on Earth. The Solid Carbon CDR solution takes advantage of the fact that CO2 reacts with basalt and changes the gas to solid rock in the form of carbonate minerals that cannot leak from the rock, thus achieving safe and secure CO2 sequestration. The feasibility and effectiveness of this concept has already been demonstrated on land. As over 90% of the world’s basalt is located in the ocean, this vast ocean basalt repository has the potential to sequester much more than is needed to keep the planet below the climate temperature target set by IPCC. THE MAIN CHALLENGES The CDR problem is under-explored to date and is both deeply technical (how to remove CO2 at scale, how and where storage will be durable, safe and measurable), and deeply social (can CDR be developed in a manner that is economically and socially responsible and widely supported?). The need is urgent, and yet rushed technology development has produced many unintended environmental and social consequences that are over-represented across vulnerable communities, particularly Indigenous communities. IN CONTRAST, THE OPPORTUNITIES ARE TREMENDOUS Sequestering CO2 in ocean basalt would address the need for durable storage of carbon, resulting in a major positive impact on the climate crisis. The team has been conducting feasibility research for 6 years using a socially responsible approach—through social science research, energy budgets, economic analysis, engagement with coastal and Indigenous communities, and consultation with regulatory agencies—to identify socio-technical solutions. This approach enables rapid and responsible technology development that follows rigorous examination of the social conditions of operation at the front end, not after the fact. Delivering CO2 to ocean basalt builds on existing ocean technology expertise at Ocean Networks Canada (ONC) and Canada’s capacity in the energy sector. Solid Carbon therefore can be scaled up quickly to meet the urgency, and help with the energy industry’s need to transition. Canada has a strategic advantage in its accessible, instrumented, and best-characterized ocean basalt location in the world. Developing Solid Carbon will keep Canada at the forefront of an emerging equitable, diverse, and sustainable trillion-dollar carbon strategy. The proposed research will enable these opportunities (in line with Canada’s new Carbon Management Strategy) by identifying the socially responsible technology approach most likely to succeed, and de-risking it so that it can advance to commercialization and be scaled-up.

Impact: Pioneering a socially responsible approach to technology development

THE APPROACH: 1) Throughout our feasibility study (2017-2023), research on social, economic, and regulatory aspects of Solid Carbon has been at the core of the team’s mandate, including a robust program of social research at the earliest stages of design so that all innovation co-emerges as both socially and technologically viable. 2) This co-emergence approach is not unique to this research team, but it is very new and not yet widely practiced; furthermore, it has itself become an outcome of the feasibility research, including published results about just, responsible, and socially viable CDR, and the development of new social engagement methods. The team will continue this approach for the proposed research to advance the social, economic, and policy conditions necessary for responsible innovation, including legitimately difficult social licence; environmental, policy, and regulatory constraints; and the methods for engaging communities.

Impact: Rapid and responsible development of a new CDR solution to safely and substantially meet the urgent need

THE APPROACH: 1) Social, economic, and engineering feasibility research (2017-2023) indicated that Solid Carbon could proceed by combining existing technologies (such as offshore injection technology) with particular social and governance conditions, using them in a new way to meet a new objective. This approach leverages existing technical, social, policy, and risk management expertise to enable relatively rapid CDR development. The proposed research will investigate a range of technically, socially, and economically feasible options for delivering CO2 into ocean basalt. 2) The project will rely on ONC’s experience in ocean research, equitable data management, and engagement with Indigenous communities; ONC’s extensive cabled monitoring network deep in the Pacific Ocean for measurement, reporting, and verification; and the Cascadia Basin, which is the best-studied ocean basalt site in the world. 3) The project will include a demonstration of CO2 injection into ocean basalt using scientific drilling and robotic technology. Demonstration is critical to de-risking the concept, a pre-condition for the social, economic, and regulatory acceptance required for commercialization and scale up.

Impact: Building a diverse, equitable Blue Economy and climate industry

THE APPROACH: 1) Dozens of post-docs and graduate students will be involved in the proposed research. The EDI strategies embedded in their recruiting and training will result in a diverse next generation of subject matter experts who will lead the CDR industry. 2) Indigenous participation in the proposed research will embed principles of ocean governance, relational responsibility, and Indigenous knowledge of the ocean into Solid Carbon and the CDR industry.

Chemical risk management as a field evaluates the safety and toxicity of a chemical by weighing the evidence of studies already produced by researchers and industries. Indigenous expertise is not considered in the formalized evaluation of chemical risk under the Canadian Environmental Protection Act (CEPA), EU Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), or the USA Toxic Substances Control Act (TSCA). This is concerning, not least because the present approach, which focuses on physiological damage to humans and other organisms, tends to objectify and pathologize already disadvantaged groups; many Indigenous Peoples are not only disproportionately exposed to chemicals but also disproportionately have their bodies subjected to testing and evaluation with little control over research design. This project seeks to bring Indigenous expertise to bear on Canadian and International chemical risk management practices as knowledge holders and not merely research subjects affected by chemicals. We hold that Indigenous knowledge about sustainability and land has important implications for chemical risk management, as do our practices of community consultation. We recognize that finding ways to meaningfully bring Indigenous expertise into existing practices is a challenge that cannot be overstated. For example, Indigenous Knowledge Systems (IKS) commonly view nature (land, water, ecosystems and associated biotic and abiotic elements) as relational. This relational worldview held by many Indigenous peoples stands in sharp contrast with the Western worldview of nature as a resource, where chemicals are viewed as isolated entities without context and generally tested one at a time for safety assessment and monitoring. The gap between a relational worldview and the more technocratic thinking underpinning present-day risk evaluation is enormous. As the new preamble to CEPA underlines the need to include Indigenous knowledge in decision-making about human and environmental health, this project is poised to close this gap. The upcoming federal requirements to recognize and combat environmental racism and the need to meet the conditions of the United Nations Declaration of the Rights of Indigenous People make this a moment of transformational opportunity. Moreover, as toxicity testing and life cycle analysis move away from animal testing and towards automation, there is a need for a paradigmatic shift in how to undertake chemical risk evaluation. This project aims to create more robust and equitable regulatory and scientific practices by effectively and meaningfully bringing Indigenous expertise into chemical management practices. Opening up existing practices surrounding chemical risk evaluation for guidance from Indigenous worldviews, methods, and values requires a critical reflection and revision of present scientific practices, including a review of the data, protocols, and methods that shape these practices. It also requires a mind shift among the people in the field, including in the practices of Health Canada and Environment and Climate Change Canada, as well as at universities and in Indigenous communities. We build on developments in Inuit Nunangatland and Aotearoa (New Zealand), where IKS has begun to be included in policy processes of relevance to chemicals management. This project will develop and expand existing chemical risk management processes using Indigenous data analysis, community consultation, Indigenous sustainability approaches, and Indigenous life cycle research. This requires bringing Indigenous research methods, Indigenous and non-Indigenous experts, Elders, and government scientists into chemical risk management from the start of the process.

Objective 1: Use Indigenous methods to investigate how existing chemical risk management information systems and practices impact the types of evidence valued and used in the evaluation of risk and chemicals management.

Objective 2: Through six interwoven subprojects, transform information systems and evaluative practices such that they are participatory with Indigenous experts from the start and include Indigenous-created evidence that reflect Indigenous values, moving beyond damage-centered data collection.

Objective 3: Build an interdisciplinary collaborative network between Indigenous and non-Indigenous experts involved in chemicals management in Canada and internationally. The team will co-create informatics models, evaluation practices, policy recommendations, protocols and associated language with Indigenous experts as well as staff in agencies in charge of chemical risk evaluation (e.g., Environment and Climate Change Canada (ECCC) and Health Canada (HC)). Working with these agencies will facilitate the inclusion of IKS into chemicals management at federal, provincial and community levels of governance. When institutionalized, these structures and systems will ensure that Indigenous knowledges are valued as part of the transformation to sustainable futures. We will collaboratively design and implement a set of training materials (e.g., a textbook, podcasts, videos) that introduce chemical risk experts and agency personnel with the power to influence the evaluation process to the value of including IKS (i.e., government staff, students, as well as professional chemists developing new substances). Transformational Change

The need for transformational change in chemical management cannot be overstated, not least as the sector is expected to double by 2030. Chemical risk management not only connects to safety but also to urgent issues like climate change. The proposed project will contribute to more effective and equitable chemical management: we will develop ways to weave Indigenous expertise into the present approach, drawing on the strength of both and finding ways to have these diverging knowledge systems support each other. Through interactions with staff in ECCC, HC and other relevant agencies, this project will lay the groundwork for better practices throughout the sector, building on these agencies’ role as leaders in the environmental-health policy space. Ultimately, the creation of better evaluation practices will influence the course of critical decisions made to reduce the dangers of irresponsible production and use of chemicals in communities across Canada and beyond. The IKS-informed chemical risk evaluation practices developed in this project will contribute to a transformation that addresses environmental racism and enhances the respect for Indigenous expertise in Canada. More than this, this project will contribute to evaluation methods that address urgent problems of persistent pollution, environmental sustainability and climate change by bringing Indigenous knowledge to the evaluation of risks.

Approximately 2.4 billion people globally are living with conditions that can benefit from rehabilitation; yet, >50% have no access to assistive technology (AT). Moreover, older adults (65+) will constitute 16% of the world population by 2050, further increasing the demands on already overstressed healthcare systems. In Canada, inequitable access to AT is evident, especially in remote and rural communities. Furthermore, older adults will constitute 25% of the Canadian population by 2050. This project will develop radically new smartwear that addresses the unmet Canadian and global AT needs. Our transformative smartwear will look like regular clothing, but will have adaptive mechanical properties that can seamlessly augment posture, balance, arm movements, and walking for persons with neuro-musculoskeletal weakness or motor impairment due to aging, congenital or acquired conditions, thereby preventing functional decline and dependence on healthcare delivery. It will also prevent work-related injuries such as those encountered by health and homecare providers, including strains, sprains, and back and shoulder injuries. The disruptive novelty of our smartwear is that its adaptive properties are built within the fibres of the fabric itself. With adaptive elements incorporated in these fibres, we are building a line of everyday clothing that can change its stiffness and shape to provide physical support and movement augmentation as needed. We are also developing within the fibres and yarns of the fabric, the technologies that will intelligently identify user intent and seamlessly change the fabric properties as needed. This smartwear will be the user’s personal physical assistant throughout their daily activities! Our smartwear will be fundamentally different from current wearable technologies that provide postural and limb support. Current state-of-the-art technologies include braces that are worn over clothing to support the trunk or joints, rigid exoskeletons for moving the arms or legs, and electrical stimulation systems to activate muscles. Although commonly available, these approaches have seen limited uptake as daily physical support systems because they are expensive, need to be custom-fit, are restrictive in their movement, are not adaptive to evolving user needs, and often cause user discomfort. Newer emerging wearable technologies for postural and limb support use “add-ons” to articles of clothing, making them cumbersome and too difficult to don and doff. Our smartwear will also move beyond function to include fashion aesthetics, making it attractive for the users. It will be light, portable, washable and affordable. Moreover, because our smartwear will look and feel like everyday clothing, it will be worn without specialized training or sophisticated labs and can thus be used anywhere and everywhere. Our smartwear will be the new revolution in AT for neuro-musculoskeletal weakness or motor impairment. It will prevent injury and augment the abilities of persons of diverse ages, genders, body sizes and cultures. Through function and fashion, our smartwear will address, in the short-term, the unmet AT needs of Canadians everywhere, improving their independence and quality of life. In the long-term, it will address the unmet global AT needs, enhancing quality of life of millions of people world-wide and facilitating their participation in education, work and leisure. Our team demonstrated that we can create fibres that can change their shape and stiffness. In Year 1, we will advance these fibres such that they can apply force to the body and sense the body’s movements using low-voltage power. We will recruit trainees, train personnel in the methodologies of co-design, secure approvals for ethics protocols, and finalize the relationships across institutions. We will then embark on 3 Aims that will be co-designed by team members and end-users through a transformative convergence of expertise across technology, textiles, art, design and social justice. The Aims have been derived by end-users and will be driven by end-users throughout the project. They will integrate technical features (sensors, actuators, power, artificial intelligence) and fashion, ensuring that smartwear seamlessly provides the strength augmentation and support needed for accomplishing daily tasks effectively, independently and safely, while also looking attractive.

Aim 1: Co-develop smartwear for the support of posture and injured joints (years 2–4). In this aim, we will develop smartwear that supports the trunk during daily activities and prevents overexertion of injured joints. This smartwear will be developed in partnership with healthcare and homecare providers who are at risk of back and shoulder injuries; older adults; people with stroke; and people with spinal cord injury (SCI) who commonly lose trunk control due to their injury.

Aim 2: Co-develop smartwear for augmentation of arm movements (years 3–5). In this Aim, we will develop smartwear that dynamically supports and augments arm movements during daily activities, including self-care activities such as brushing teeth or hair, reaching, and carrying a load. This smartwear will be developed in partnership with older adults and people with muscular dystrophy, SCI, or stroke who experience decreases in arm strength.

Aim 3: Co-develop smartwear for augmentation of standing and walking (years 4–6). In this Aim, we will develop smartwear for the legs that can dynamically support sit-to-stand activities, balanced standing, and walking. We will develop this in partnership with the same end-user communities in Aim 2, who have weakened muscles that reduce their ability to stand independently from a sitting position and increase their risk of catastrophic falls while walking. Smartwear will reduce the effort involved in sit-to-stand transitions, and enable functionally long durations of standing and functionally long distances of walking. Broad knowledge exchange and dissemination will be through 2 public art and technology festivals in years 3 and 6, that will showcase smartwear. They will be thematically structured around the iterative developments, progressing from passivity and discretion smartwear in postural support to strength and movement. In partnership with industry, various smartwear products will be manufactured and approved for sales in Canada during the funding period, thus facilitating widespread implementation of smartwear nationally. The initial impacts and short-term benefits will be expanded soon after, providing health benefits and reductions in healthcare costs nation-wide. The long-term benefits will be manufacturing and availability of smartwear globally, resulting in a large-scale transformation in the lives of millions of people living with movement limitations who currently have little or no access to assistive technologies.

Indigenous communities and healthcare leaders across Canada are faced with challenges associated with aging, including higher rates of dementia and its risk factors at younger ages in Indigenous populations compared with other populations in Canada. These trends are underpinned by historical and ongoing impacts of colonization on Indigenous health. This context requires urgent community self-determined approaches to prevent dementia, diagnose dementia, and promote the quality of life for people living with dementia and their care communities. The diagnosis of dementia conventionally requires standardized assessments of cognition and function. However, Indigenous Peoples have distinct cultural, relational perspectives on dementia, aging, and daily function that influence the ways that these concepts are understood and should be measured. The acceptability of conventional and standardized approaches to assessment is also influenced by strong associations between “assessment” and loss in Indigenous communities; in many cases, outside assessment processes have resulted in loss of children, loss of autonomy, or loss of dignity, at both individual and collective levels.

The overall long-term goal of this project is to decolonize brain health assessment in Indigenous communities and support Indigenous centred brain health assessment, education, training for healthcare providers, and supportive care. We are working with the concept of building a “Bundle”, which, for many Indigenous Peoples, is a sacred set of items and medicines that an individual has gathered and that they care for. We will create a Bundle that contains assessment tools, training materials, and guidance that a community can use to address rising rates of dementia. To do this we will: 1. Integrate diverse Indigenous and Western biomedical perspectives to develop a new approach to wholistic brain health assessment 2. Build consensus on the components of a decolonized brain health assessment Bundle through extensive Indigenous community engagement and leadership 3. Develop a proposed culturally responsive brain health assessment Bundle 4. Test and refine the assessment Bundle for reliability and validity 5. Return the Bundle to Indigenous communities and assist in the spread and uptake of the Bundle We are a team from eight Indigenous community organizations and fourteen universities across four provinces who bring knowledge from diverse First Nations, Métis, and Western disciplinary perspectives. We are weaving interdisciplinary perspectives and Indigenous knowledge, grounded in a research paradigm that prioritizes relational accountability. Our weaving approach enables us to balance relational research and rigour in our methods to create scientifically and culturally relevant brain health assessments. We have organized our workplan in seasonal cycles over six years, with Spring being a season of distinct community gatherings in each of the six sites and Summer being a time for iterative community-based data collection and analysis. We will then all come together each Fall in a national gathering to share and build consensus. Winter will be a time of synthesis, communication, and preparation for the next cycle of community-based data collection and consensus. The transformative nature of this work lies in its wholistic, culturally grounded, and community-led approach to rethinking approaches to brain health. The impact of this work will be to decolonize brain health assessment and to provide Indigenous communities with safe and accurate tools, training and processes to support people through their brain health trajectories. A significant anticipated outcome is earlier and more accurate diagnosis of dementia, which will result in more meaningful connection to appropriate supports and services, which will change the journey for Indigenous people living with dementia and their care communities. Better diagnosis will also provide better population-level information on dementia risk and diagnosis, which will support Indigenous self-determined solutions to this emerging concern.