Ottawa, Ontario — Friday July 15, 2022
Three CHEO Research Institute projects received Canadian Institutes of Health Research (CIHR) grants from the Spring 2022 Project Grant competition. Two of these applications ranked in the Top 5 within their panel and one was funded through the priority announcement: Institute of Musculoskeletal Heath and Arthritis. Overall, the CHEO Research Institute had a 25 per cent success rate in this competition (CIHR average is 19.3 per cent).
Project: SUNRISE International Study of Movement Behaviours in the Early Years
Amount/time period funded: $1,514,000 over 3.5 years.
Nominated Principal Investigator: Mark Tremblay
Co-applicants: Emily Bremer, Guy Faulkner, Alex A Florindo, Nicholas O Kuzik, Himangi Lubree, Linda S Pagani, Tawonga W Mwase-Vuma, Anthony D Okely, John J Reilly, Patricia Tucker, Olga Antsygina, Hilary A Caldwell, Valerie L Carson.
Overview: This research project will explore movement behaviours (combined and integrated physical activity, sedentary behaviour, sleep) and examine the relationships between movement behaviours and physical, cognitive, and social-emotional development in urban and rural children in: Canada, Brazil, India, and Malawi.
The early years (0-5 years) is a critical and sensitive period for lifelong development, as key experiences or missed experiences can alter a child’s developmental potential. Thus, international efforts have focused on ensuring children <5 years are developmentally on track. Unfortunately, our understanding of childhood development is limited and predominantly informed by research on children from high-income countries and urban settings.
One set of exposures with potential benefits to childhood development are physical activity, sedentary behaviour, and sleep—collectively termed movement behaviours— but are understudied worldwide. Our group was the first to recognize the importance of movement behaviours when we developed the Canadian 24-hour movement guidelines for early years children. Subsequently, we guided the WHO to the creation of global 24-hour movement behaviour guidelines. While the benefits to children’s lifelong development from single movement behaviours (e.g. physical activity) has been demonstrated, little is known about the ideal distribution or composition of movement behaviours in a 24-hour day for optimal development. Further, this lack of information is particularly pronounced in rural settings and low and middle-income countries (LMIC), exacerbating already existing global inequities.
This study will directly respond to calls for international surveillance of children’s movement behaviours and development. The examination across the included countries will improve our understanding in rural and LMICs, ultimately leading to a richer, more global and equitable understanding of the universal and culturally specific aspects of children’s movement behaviours and development.
Project: Developing collaboratively a shared decision making tool for home-based videoconferencing versus in person care in child and youth mental health
Amount/time period funded: $424,576 over 2 years
Nominated Principal Investigator: Philippe Robaey
Co-Applicants: Suneeta Monga, Alice Charach, Avril Deegan, Ellen L Lipman, Christopher Wilkes, Allison Crawford, Lily Hechtman, Leslie A Campbell, Alexa L Bagnell, Katharine Thomson, Susan Baer, Evangelia L Amirali, Sabina Abidi, Iliana Ortega, Purnima Sundar, Vivian W Tsang, Elyse Schipper, Rachel C Kronick, Jill E Chorney.
Overview: In response to the COVID-19 pandemic, the closure of Child and Youth Mental Health (CYMH) outpatient clinics and the switch from in-person to virtual care has resulted in an unprecedented mass adoption of telemental health (TMH) through home-based videoconferencing (HBVC), using personal devices (e.g., computers, tablets, smartphones).
The decision to HBVC or in-person care should not be made just by asking: “Do you want to meet in person or by HBVC next time?” but has to be properly supported and documented through a SDMT.
This project will develop a shared decision making tool (SDMT) to support this decision, which is the cornerstone of the hybrid model. The focus will be on individual/family outpatient consultations including structured or manualized group/family therapy or assessment. The deliverables will be a SDMT supported by an educational website. This will allow a successful adoption of the hybrid model, which is arguably one of the most significant changes in CYMH services in recent decades with potential to improve delivery and quality of care, costs, patient engagement, and access inequities.
Project: The role of Pannexin 1 in Skeletal Muscle Regeneration and Duchenne Muscular Dystrophy
Amount/time period funded: $100,000 for one year
Nominated Principal Investigator: Kyle Cowan
Co-Applicants: Jasmin Bernard
Overview: Skeletal muscle has a tremendous capacity to regenerate in healthy individuals. However, this regenerative potential is dramatically impaired in Duchenne muscular dystrophy (DMD), resulting in muscle weakness, damage, and atrophy. DMD is the most common form of muscular dystrophy. There is no cure for this devastating disorder, resulting in the premature death of this vulnerable population. While the underlying cause of DMD is the absence of dystrophin, the specific factors that perpetuate disease progression need to be better understood to identify potential therapeutic strategies.
We have found that pannexin 1 (PANX1; Panx1 in rodents) channels, well known for their role in ATP release, play a key role in myogenesis. Fiber typing and enhancement of contractile force also depend upon Panx1-mediated ATP release. PANX1 is expressed in satellite cells (SC), which are the cells responsible for muscle regeneration. Our data indicate that Panx1-/- mice have smaller myofibers, reduced grip strength, a lower number of SCs combined with an altered myogenic differentiation capacity. Panx1 targeting also impaired muscle regeneration in vivo. In murine models of DMD, Panx1 levels decrease as the disease worsens. PANX1 levels and channel activity were also reduced in myoblasts from DMD patients. Our recent data show that dystrophic (mdx) mice that are deficient in Panx1 (Panx1-/-/mdx) have reduced lean mass, grip strength, and muscle force. Their muscles have a reduced number of fibers and show enhanced tissue damage and disease severity. Notably, our preliminary data suggest that the Panx1-/-/mdx mice have a significantly shorter lifespan. We thus hypothesize that Panx1 channels play a significant role in regulating SC function and skeletal muscle regeneration, as well as in DMD disease progression by regulating processes leading to muscle degeneration, damage, and weakness. As PANX1 over-expression increased the myogenic capacity of myoblasts from DMD patients, we also suggest that increasing Panx1 levels in dystrophic muscles may have therapeutic potential by promoting the formation of new muscle fibers.
The Cowan and Jasmin teams bring complementary expertise in pannexin biology, translational research, myogenesis, DMD pathology, and extensive experience in mouse models of DMD to ensure that these studies provide insights into the role of Panx1 in muscle regeneration and DMD, and its therapeutic potential to improve the outcome for DMD patients.
View the complete list of the CIHR Project Grant: Spring 2022 results.