A Short Antisense Oligonucleotide Ameliorates Symptoms of Severe Mouse Models of Spinal Muscular Atrophy
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The Department of Biomedical Sciences aims to provide knowledge of anatomy and physiology in order to understand the mechanisms and treatment of animal diseases. Additionally, it seeks to teach the understanding of drug-action for rational drug-therapy, as well as toxicology, pharmacodynamics, and clinical drug administration.
History
The Department of Biomedical Sciences was formed in 1999 as a merger of the Department of Veterinary Anatomy and the Department of Veterinary Physiology and Pharmacology.
Dates of Existence
1999–present
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- College of Veterinary Medicine (parent college)
- Department of Veterinary Anatomy (predecessor, 1997)
- Department of Veterinary Physiology and Pharmacology (predecessor, 1997)
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Abstract
Recent reports underscore the unparalleled potential of antisense-oligonucleotide (ASO)-based approaches to ameliorate various pathological conditions. However, in vivo studies validating the effectiveness of a short ASO (survival motor neuron 1 (SMN1) gene. Correction of aberrant splicing of the remaining paralog, SMN2, can rescue mouse models of SMA. Here, we report the therapeutic efficacy of an 8-mer ASO (3UP8i) in two severe models of SMA. While 3UP8i modestly improved survival and function in the more severe Taiwanese SMA model, it dramatically increased survival, improved neuromuscular junction pathology, and tempered cardiac deficits in a new, less severe model of SMA. Our results expand the repertoire of ASO-based compounds for SMA therapy, and for the first time, demonstrate the in vivo efficacy of a short ASO in the context of a human disease.
Comments
This article is published as Keil, Jeffrey M., Joonbae Seo, Matthew D. Howell, Walter H. Hsu, Ravindra N. Singh, and Christine J. DiDonato. "A short antisense oligonucleotide ameliorates symptoms of severe mouse models of spinal muscular atrophy." Molecular Therapy-Nucleic Acids 3 (2014): e174. DOI: 10.1038/mtna.2014.23. Posted with permission.