Neuromuscular disease

Established in 1999, the University of Ottawa Centre for Neuromuscular Disease (CNMD) was mandated "to advance the understanding of neuromuscular and related disorders and enhance human health through the development and implementation of novel therapies." CNMD members study all aspects of neuromuscular function and dysfunction and conduct activities such as basic research, translational medicine and clinical research.

Our Collaborative Partnership Team, through the uOBMRI, has proudly provided funding to support 5 STaR trainee Scholarships for Neuromuscular Disease Research projects annually.

The uOBMRI also supported the 4th Ottawa International Conference on Neuromuscular Biology, Disease and Therapy in October 2019. This Conference was hosted by the Center for Neuromuscular Disease and highlighted advances in all aspects of neuromuscular disease (NMD) research, including novel techniques to diagnose NMD, biology of disease pathogenesis, basic muscle and stem cell biology, expanding clinical phenotypes and promising therapies to treat these devastating disorders. The Conference was structured for both basic researchers and clinicians and featured internationally-recognized invited speakers and selected abstract presentations. Sessions were organized to include basic, translational and clinical presentations, in order to engage all attendees regardless of background or training, with four breakout sessions focusing exclusively on fundamental basic biology or clinical studies. The Conference was a huge success! It attracted 300 experts and trainees from all around the world.

Under the uOBMRI umbrella, CNMD researchers have united to focus their expertise on B3 for NMD: Bench to Bedside and Back – Transformative Discoveries Leading to Care in Neuromuscular Disease. This project creates a streamlined process to implement the bench (preclinical) to bedside (next generation sequencing, clinical trials) and back (clinically informed basic research) approach in order to develop therapies for patients with NMD. This project includes gene discovery, disease-state pathogenesis, therapy development, natural history and clinical trials. Other B3 for NMD projects include:

Next-generation sequencing for molecular diagnosis and identification of novel genes causing NMD

Next-generation sequencing examines hundreds to thousands of genes simultaneously, providing an efficient, effective and cost-saving approach to molecular diagnosis for patients with inherited NMD. These methods rapidly identify mutations in novel genes, leading to discovery of the molecular mechanisms behind the disease state.

Preclinical characterization of normal muscle development and pathophysiological mechanism of atrophy

Preclinical research provides the foundation for discoveries that improve the lives of patients with NMD. The identification of individual cellular and molecular events for normal muscle differentiation drives the development of regenerative-based therapies. The uOBMRI will:

• Investigate the molecular pathways guiding cell fate determination of muscle stem cells
• Elucidate the complex regulatory networks governing muscle and neuronal cell differentiation
• Examine the neuromuscular junction—the crucial point of contact between the motor neuron and muscle—in the normal and diseased states

Therapeutic drug discovery to treat NMD

Although many NMDs were previously incurable, recent breakthroughs in the molecular pathogenesis of diseases caused by a single gene and acquired disorders are now revealing potential targeted disease-modifying therapies that may improve muscle health and prevent disability. CNMD researchers will examine novel or repurposed drug compounds to identify promising therapies that can be rapidly moved into local and multi-centre clinical trials.

Clinical research and clinical therapeutic trials to treat NMD

To build on the world-renowned preclinical research conducted in Ottawa, CNMD will translate basic discoveries to the clinic through the implementation of mechanisms that will support clinical trials. We will also create a streamlined process for tissue bio-banking, which provides essential material for basic researchers to reveal the underlying disease pathogenesis, guiding the development of the next generation of targeted therapeutics (the "and back" part of our mission).