B3 for NMD: Bench to Bedside and Back

The B3 for NMD creates a streamlined approach to develop the Bench (preclinical and laboratory characterization) to Bedside (clinical and imaging assessment) and Back (biomarker, diagnostics and therapy development) approach to develop transformative therapies for patients with rare NMDs. This study focuses on assessing current diagnostic techniques and disease characterization of difficult-to-diagnose NMDs including Motor Neuron Disease (e.g. ALS), Neuromuscular Junction Disorders, Neuropathies, Myopathies.

Activity 1: Improve Diagnosis: Identification of rare and novel genes causing NMD with next generation sequencing and develop imaging modalities and biomarkers to aid in diagnosis.

A collaborative research team of clinicians, informaticians, and scientists has been formed to rapidly identify the genes and the autoimmune antibodies responsible for a wide spectrum of NMD present in the Canadian population, as well as to explore mechanisms causing these disorders. In addition, novel genetic and biomarker approaches are needed to facilitate diagnosis and permit the identification of mutations in novel genes, leading to discovery of the molecular mechanisms underlying the NMD disease state. Novel diagnostic techniques that examine thousands of genes (e.g. exome/genome sequencing), protein expression (e.g. RNA sequencing) and/or serum biomarkers (e.g. exosomes) will be assessed to provide a more rapid diagnosis for patients with NMD. In addition, imaging characteristics for these rare diseases (MRI, Muscle/Nerve Ultrasound/nerve conduction studies) need to be assessed and compared in order to provide an efficient, effective and cost-savings approach to diagnosis for patients with inherited or sporadic NMD.

Activity 2. Disease Characterization: Identifying pathophysiological mechanisms in NMD

Preclinical research provides the foundation for discoveries that improve lives for patients with NMD. The identification of cellular and molecular events that govern normal muscle and nerve differentiation drives the development of regenerative-based therapies, whereas the characterization of the disease state uncovers new therapeutic targets for disease intervention. Although many NMDs were previously incurable, recent breakthroughs in the molecular pathogenesis of monogenic and acquired disorders are now revealing potential targeted disease-modifying therapies that may improve muscle health and prevent disability. The goal is to assess clinical samples such as blood, skin/muscle biopsies, cerebrospinal fluid obtained through collaboration with NeuroMuscular Centre clinicians and researchers to help develop effective novel/known drug compounds that may act as promising therapies that, in the future, can be rapidly moved into local and multicenter clinical trials.

• To characterize disease mechanisms to advance potential therapies of tomorrow. [Срок оценки: 5 years]