Subcutaneous administration of TC007 reduces disease severity in an animal model of SMA.

BMC Neuroscience
Virginia B MattisC L Lorson

Abstract

Spinal Muscular Atrophy (SMA) is the leading genetic cause of infantile death. It is caused by the loss of functional Survival Motor Neuron 1 (SMN1). There is a nearly identical copy gene, SMN2, but it is unable to rescue from disease due to an alternative splicing event that excises a necessary exon (exon 7) from the majority of SMN2-derived transcripts. While SMNDelta7 protein has severely reduced functionality, the exon 7 sequences may not be specifically required for all activities. Therefore, aminoglycoside antibiotics previously shown to suppress stop codon recognition and promote translation read-through have been examined to increase the length of the SMNDelta7 C-terminus. Here we demonstrate that subcutaneous-administration of a read-through inducing compound (TC007) to an intermediate SMA model (Smn-/-; SMN2+/+; SMNDelta7) had beneficial effects on muscle fiber size and gross motor function. Delivery of the read-through inducing compound TC007 reduces the disease-associated phenotype in SMA mice, however, does not significantly extend survival.

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Jul 8, 2008·Neuroscience Letters·Virginia B MattisChristian L Lorson
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Citations

Feb 26, 2011·Transgenic Research·Monique A LorsonKevin D Wells
Apr 16, 2010·Human Molecular Genetics·Christian L LorsonMonir Shababi
Feb 8, 2013·Human Molecular Genetics·Melissa S CobbChristian L Lorson
Nov 20, 2012·Future Medicinal Chemistry·Monique A Lorson, Christian L Lorson
Aug 29, 2012·Future Medicinal Chemistry·Jonathan J Cherry, Elliot J Androphy
Jul 30, 2014·Future Medicinal Chemistry·Matthew D HowellRavindra N Singh
Apr 26, 2015·Expert Opinion on Investigational Drugs·Anna KaczmarekMarkus Riessland
Jun 8, 2012·Critical Reviews in Biochemistry and Molecular Biology·Kim M KeelingDavid M Bedwell
Jun 10, 2015·Neuromuscular Disorders : NMD·Ashlee W Harris, Matthew E R Butchbach
Jul 24, 2012·Neuroscience Letters·Virginia B MattisChristian L Lorson
Sep 3, 2013·Biochimica Et Biophysica Acta·Joonbae SeoRavindra N Singh
Jul 30, 2014·MedChemComm·Marina Y FossoSylvie Garneau-Tsodikova
Feb 20, 2016·Experimental Neurology·Matthew E R ButchbachArthur H M Burghes
Dec 12, 2019·The Cochrane Database of Systematic Reviews·Renske I WadmanAlexander Fje Vrancken
Feb 2, 2020·The Cochrane Database of Systematic Reviews·Renske I WadmanAlexander Fje Vrancken
Oct 15, 2019·Frontiers in Genetics·Alireza ShahryariHeiko Lickert
Jul 8, 2020·International Journal of Molecular Sciences·Valentino BezzerriMarco Cipolli
Mar 23, 2021·Cellular and Molecular Life Sciences : CMLS·Patrícia Martins-Dias, Luísa Romão

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Methods Mentioned

BETA
SMA

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