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Guidance on Gene Replacement Therapy in Spinal Muscular Atrophy: A Canadian Perspective

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source: Canadian Journal of Neurological Sciences

year: 2021

authors: Maryam Oskoui, Hernan Gonorazky, Hugh J. McMillan, James J. Dowling, Reshma Amin, Cynthia Gagnon, Kathryn Selby


Spinal muscular atrophy (SMA) is the second most common autosomal recessive disorder in childhood. It is caused by deletions or mutations in the survival motor neuron 1 (SMN1) gene and characterized by degeneration of motor neurons leading to progressive muscle weakness and atrophy. A similar backup gene called survival motor neuron 2 gene (SMN2) acts as a disease modifier, with increasing number of SMN2 copies associated with milder phenotype.

Considerable advances in the last 10 years have led to the development of disease-modifying therapies in SMA which have transformed outcomes. Therapeutic approaches use different mechanisms of action, routes of administration, and dose scheduling. The core treatments are SMN-dependent and include SMN1 gene replacement or SMN2 pre-mRNA splicing modulation.

With all therapies, the highest efficacy is seen when administered pre-symptomatically, prompting the need for SMA newborn screening programs. Nusinersen was the first drug approved for SMA treatment in Canada in June 2017. It is administered intrathecally at 4 monthly intervals after 4 initial loading doses. Another SMN2 splicing modulator is risdiplam which is administered orally on a daily basis.


organization: Research Institute of the McGill University Health Centre, Canada; The Hospital for Sick Children, Centre for Computational Medicine, USA; Children’s Hospital of Eastern Ontario Research Institute, Canada; Department of Paediatrics, University of Toronto, Canada; The Hospital for Sick Children, Division of Respiratory Medicine, Canada; The University of British Columbia, Division of Pediatric Neurology, Canada; Centre de recherche Charles-Le Moyne-Saguenay-Lac-Saint-Jean sur les innovations en santé (CRCSIS), Canada

DOI: 10.1017/cjn.2021.125

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