Abstract
Spinal muscular atrophy (SMA) is one of the most common genetic causes of infantile death arising due to mutations in the SMN1 gene and the subsequent loss of motor neurons. With the discovery of the intronic splicing silencer N1 (ISS-N1) as a potential target for antisense therapy, several antisense oligonucleotides (ASOs) are being developed to include exon 7 in the final mRNA transcript of the SMN2 gene and thereby increasing the production of spinal motor neuron (SMN) proteins. Nusinersen (spinraza), a modified 2′-O-methoxyethyl (MOE) antisense oligonucleotide is the first drug to be approved by Food and Drug Agency (FDA) in December of 2016. Here we briefly review the pharmacological relevance of the drug, clinical trials, toxicity, and future directions following the approval of nusinersen.
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Acknowledgments
This work is supported by the Slipchuk SMA Research Fund, Muscular Dystrophy Canada, the Friends of Garrett Cumming Research Fund, the HM Toupin Neurological Science Research Fund, the Canadian Institutes of Health Research (CIHR), the Alberta Innovates: Health Solutions (AIHS), the Canada Foundation for Innovation (CFI), the Alberta Advanced Education and Technology, and the Women and Children’s Health Research Institute (WCHRI).
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Goodkey, K., Aslesh, T., Maruyama, R., Yokota, T. (2018). Nusinersen in the Treatment of Spinal Muscular Atrophy. In: Yokota, T., Maruyama, R. (eds) Exon Skipping and Inclusion Therapies. Methods in Molecular Biology, vol 1828. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8651-4_4
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DOI: https://doi.org/10.1007/978-1-4939-8651-4_4
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