This joint research program connects the University of Ottawa Éric Poulin Centre for Neuromuscular Disease (CNMD) and the Université Claude Bernard Lyon 1 Laboratory of Pathophysiology and Genetics of Neuron and Muscle (PGNM) – two leading institutes in neuromuscular disease research with complementary expertise in basic and clinical research.
The 2025 competition selected four collaborative projects, each receiving $20,000 CAD from the University of Ottawa and €20,000 EUR from Université Claude Bernard Lyon 1. The funded projects cover a range of neuromuscular research topics, including: the role of the integrated stress response in mitochondrial disorders; the function of a newly identified gene linked to neuromuscular and neurodevelopmental disorders involving hypotonia and epilepsy; the contribution of muscle stem cell mitochondria to myonuclear accretion and aging; and the testing of antioxidant based therapies to reduce disease features in spinal muscular atrophy.
These projects were reviewed, ranked, and awarded through a competitive process that emphasized research excellence, synergy and collaboration, innovation, and project sustainability. As part of the application process, applicants provided confirmation of completed SGBA+ (Sex and Gender Based Analysis) or IDEAS (inclusivity, diversity, equity, accessibility, and social justice) training, reflecting the Faculty’s commitment to these principles.
2025 CNMD-PGNM Collaborative Research Grant Awardees
Dr. David Dyment (Department of Pediatrics, uOttawa; CHEO-RI) & Dr. Binnaz Yalcin (Institut NeuroMyoGène, Claude Bernard Université Lyon 1).
Studying WDR47-related neuromuscular disease in human and mice
Rare genetic diseases remain a major clinical challenge, with many patients lacking a clear molecular diagnosis. This project focuses on WDR47, a newly identified gene linked to neuromuscular and neurodevelopmental disorders characterized by low muscle tone (hypotonia) and seizures. By integrating human genetic studies with mouse models, this collaborative project aims to better understand how both single copy (mono allelic) and two copy (bi allelic) changes in WDR47 lead to disease. To achieve this, the team will expand and carefully characterize patient cohorts to define genotype–phenotype relationships and will study knockout and knock in mouse models to uncover the biological mechanisms involved. Together, this work has the potential to advance understanding of WDR47 related disorders, improve diagnosis for affected individuals, and lay the groundwork for future treatments.
Dr. Izabella Pena (Department of Cellular and Molecular Medicine, uOttawa; CHEO-RI) & Dr. Hélène Puccio (Institut NeuroMyoGène, Claude Bernard Université Lyon 1).
Investigation of integrated stress response activation across mitochondrial disorders
Congenital Sideroblastic Anemia and Friedreich Ataxia are inherited disorders that disrupt heme and iron–sulfur cluster biogenesis—essential mitochondrial pathways that regulate iron use for energy production and cellular health. Although caused by different genetic defects, this project proposes that these diseases share a common underlying mechanism: chronic activation of the heme regulated inhibitor (HRI) kinase–mediated integrated stress response (ISR) driven by iron imbalance. In this project, the team will test the role of HRI, perform metabolomic analyses, and dissect the molecular mechanisms involved. Targeting this shared pathway has the potential to uncover new therapeutic strategies for rare mitochondrial diseases and establish ISR modulation as a broader treatment paradigm.
Dr. Mireille Khacho (Department of Biochemistry, Microbiology, and Immunology, uOttawa) & Dr. Anita Kneppers (Institut NeuroMyoGène, Claude Bernard Université Lyon 1)
Muscle stem cell mitochondria in myonuclear accretion and aging
Aging skeletal muscle undergoes profound structural and metabolic decline, culminating in sarcopenia – the progressive, age-related loss of muscle mass, strength and function. Emerging evidence indicates that muscle stem cells (MuSCs) do more than add new nuclei to growing muscle fibers—they also transfer mitochondria, suggesting a novel mechanism linking muscle growth to metabolic plasticity.
This project studies how OPA1, a protein that controls mitochondrial shape and function, influences muscle stem cell contributions to muscle fibers. Specifically, the team will examine how mitochondrial behavior in MuSCs affects the addition of new nuclei, the transfer of mitochondria into muscle fibers, and the muscle fiber’s ability to adapt its metabolism. Using genetic models in which OPA1 function is disrupted, the team will determine how faulty mitochondrial regulation in MuSCs leads to muscle fiber dysfunction and contributes to sarcopenia. Overall, this work aims to reveal a previously unrecognized link between muscle stem cells, mitochondria, and muscle aging.
Dr. Rashmi Kothary (Department of Medicine, uOttawa; OHRI) & Dr. Ambra Giglia-Mari (Institut NeuroMyoGène, Claude Bernard Université Lyon 1)
Antioxidant-based therapeutic to mitigate pathological features in Spinal Muscular Atrophy
Spinal muscular atrophy (SMA) remains incurable despite major advances in therapies that restore survival motor neuron (SMN) gene function, underscoring the need for complementary strategies to further improve patient outcomes. Recent studies indicate that SMN-deficient cells are highly sensitive to oxidative stress, prompting interest in antioxidant compounds as potential adjuvant treatments. Growing evidence also suggests that SMA is a systemic disorder affecting multiple organs, including neuromuscular and cardiac tissues. This proposal examines selected antioxidant molecules – identified through a targeted cellular screen – in the Smn2B/- mouse model of SMA. The team will evaluate their effects on neuromuscular, cardiac, molecular, and metabolic phenotypes, assess potential synergistic interactions, and explore the impact of maternal treatment during gestation. This work aims to establish a strong foundation for integrating antioxidant strategies into existing SMA therapeutic regimens. By investigating both neuromuscular and cardiac involvement, this study will provide insight into the role of systemic oxidative stress in SMA pathology and evaluate how antioxidant interventions may mitigate disease manifestations.