Journal article
Combination of valproic acid and morpholino splice-switching oligonucleotide produces improved outcomes in spinal muscular atrophy patient-derived fibroblasts
A Farrelly-Rosch, CL Lau, N Patil, BJ Turner, F Shabanpoor
Neurochemistry International | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2017
Abstract
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality worldwide, is characterised by the homozygous loss of the survival motor neuron 1 (SMN1) gene. The consequent degeneration of spinal motor neurons and progressive atrophy of voluntary muscle groups results in paralysis and eventually premature infantile death. Humans possess a second nearly identical copy of SMN1, known as SMN2. However, SMN2 produces only 10–20% functional SMN protein due to aberrant splicing of its pre-mRNA that leads to the exclusion of exon 7. This level of SMN is insufficient to rescue the phenotype. Recently developed splice-switching antisense oligonuclotides (SSO) have shown great promise in..
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Awarded by Motor Neurone Disease Research Institute of Australia
Funding Acknowledgements
We would like to thank Prof. Philip M Beart for his help with revising the manuscript. FS is a recipient of a CJ Martin Fellowship from the Australian National Health and Medical Research Council (APP1034300) and also acknowledges support by the Bethlehem Griffith Research Foundation (BGRF1501) and support by Early Career Research grant (704-6496, University of Melbourne). Work in the laboratory of BJT was funded by the Australian National Health and Medical Research Council (1104299), Stafford Fox Medical Research Foundation, MND Research Institute of Australia (1609) and Cure for MND Foundation. The Florey Institute of Neuroscience and Mental Health acknowledges the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant.