A5057859022- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Congenital Anomalies and Fetal Surgery
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Mechanical Circulatory Support Devices
- Muscle Physiology and Disorders
- Cardiac Structural Anomalies and Repair
Ottawa Hospital Research Institute
2020-2024
Ottawa Hospital
2020-2024
University of Ottawa
2020-2024
Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by mutations in the SMN1 gene. Despite development of various therapies, outcomes can remain suboptimal SMA infants and duration such therapies are uncertain. SMN2 paralogous gene that mainly differs from C•G-to-T•A transition exon 7, resulting skipping 7 most transcripts production only low levels survival motor neuron (SMN) protein. Genome editing technologies targeted to mutation could offer therapeutic strategy...
Abstract Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by motor neuron loss and skeletal muscle atrophy. SMA caused the of SMN1 gene low SMN protein levels. Current therapies work increasing in body. Although regarded as a disorder, growing evidence shows that several peripheral organs contribute to pathology. A therapy treatment, onasemnogene abeparvovec, being explored clinical trials via both systemic central nervous system (CNS) specific...
BackgroundMouse models of mild spinal muscular atrophy (SMA) have been extremely challenging to generate. This paucity model systems has limited our understanding pathophysiological events in milder forms the disease and effect SMN depletion during aging.MethodsA mouse SMA, termed Smn2B/−;SMN2+/−, was generated by crossing Smn−/−;SMN2 Smn2B/2B mice. new characterized using behavioral testing, histology, western blot, muscle-nerve electrophysiology as well ultrasonography study classical SMA...
Background: The liver is a key metabolic organ, acting as hub to metabolically connect various tissues. Spinal muscular atrophy (SMA) neuromuscular disorder whereby patients have an increased susceptibility developing dyslipidaemia and steatosis. It remains unknown whether fatty due intrinsic or extrinsic impact of survival motor neuron (SMN) protein depletion. Methods: Using adeno-associated viral vector with specific promoter (albumin), we restored SMN levels in the alone Smn2B/- mice,...
Spinal Muscular Atrophy (SMA) is an inherited neurodegenerative disease caused by the loss or mutation of survival motor neuron 1 (SMN1) gene. Though classically regarded as a disorder, reports are increasingly describing involvement non-neuronal organs in SMA. The Smn2B/- mouse model SMA that displays peripheral phenotype including metabolic defects. Here, we characterized several neuronal and defects throughout development to better understand progression relationship between tissue We...
Abstract Spinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the SMN1 gene. Although lower motor neurons are primary target, there evidence that peripheral organ defects contribute to SMA. Current SMA gene therapy uses single, high titre intravenous bolus AAV9-SMN resulting in impressive, yet limited amelioration clinical phenotype. However, risks this treatment include liver toxicity. Intrathecal administration under trial but was interrupted due safety concerns...