SOD1 silencing in motoneurons or glia rescues neuromuscular function in ALS mice

Annals of Clinical and Translational Neurology
Elisabeth DirrenPatrick Aebischer

Abstract

Amyotrophic lateral sclerosis is an incurable disorder mainly characterized by motoneuron degeneration. Mutations in the superoxide dismutase 1 (SOD1) gene account for 20% of familial forms of the disease. Mutant SOD1 exerts multiple pathogenic effects through the gain of toxic properties in both neurons and glial cells. Here, we compare AAV-based gene therapy suppressing expression of mutant SOD1 in either motoneurons or astrocytes. AAV vectors encoding microRNA against human SOD1 were administered to (G93) (A)SOD1 mice either by intracerebroventricular injections in pups or by lumbar intrathecal injections in adults. Vector systems were designed to suppress SOD1 expression predominantly in either spinal motoneurons or astrocytes. Electrophysiological and behavioral tests were performed on treated animals to evaluate disease progression. Following vector injection in (G93) (A)SOD1 pups, efficient silencing of SOD1 expression was achieved in motoneurons and/or astrocytes. Most complete protection of motor units was obtained when targeting human SOD1 predominantly in motoneurons. Suppressing SOD1 mainly in astrocytes led to preserved muscle innervation despite only partial protection of spinal motoneurons. In both cases, injecti...Continue Reading

References

Jun 3, 2006·Science·Séverine BoilléeDon W Cleveland
Feb 5, 2008·Nature Neuroscience·Koji YamanakaDon W Cleveland
Feb 15, 2008·Amyotrophic Lateral Sclerosis : Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases·Sean ScottJames A Heywood
Feb 29, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dick JaarsmaCasper C Hoogenraad
Oct 22, 2008·Nature Neuroscience·Angelo C LeporeNicholas J Maragakis
Feb 5, 2009·Annals of Neurology·Jeffrey D Rothstein
Sep 5, 2009·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Jenny S HenkelStanley H Appel
Apr 7, 2010·Annual Review of Neuroscience·Kevin C KanningChristopher E Henderson
Oct 22, 2010·Human Molecular Genetics·Lijun WangRaymond P Roos
Jul 19, 2011·Neurology Research International·Jurate Lasiene, Koji Yamanaka
Aug 21, 2012·Acta Neuropathologica·Ammar Al-ChalabiLeonard H van den Berg
Sep 7, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kevin D FoustBrian K Kaspar
Sep 7, 2014·Brain : a Journal of Neurology·Axel FreischmidtJochen H Weishaupt

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Citations

Dec 30, 2015·Human Gene Therapy·Florie BorelChristian Mueller
May 7, 2016·Neuroscience Letters·Pablo RozasDanilo B Medinas
Jun 29, 2016·Molecular Neurobiology·Maria Sara Cipolat MisStefania Corti
Jun 9, 2016·Human Gene Therapy·Michaël HocquemillerNathalie Cartier
Aug 18, 2016·Frontiers in Molecular Neuroscience·Lorelei Stoica, Miguel Sena-Esteves
Aug 11, 2016·Neuroscience Letters·Brigitte van Zundert, Robert H Brown
Oct 19, 2016·Annals of Clinical and Translational Neurology·Ioanna EleftheriadouNicholas D Mazarakis
Dec 8, 2017·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Ji-Ung Park, Sung-Tack Kwon
Mar 30, 2018·Human Gene Therapy Methods·Dan WangGuangping Gao
Nov 21, 2018·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration
Feb 6, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hongxia LeiPatrick Aebischer
Dec 23, 2017·Frontiers in Molecular Neuroscience·Andrew P Tosolini, James N Sleigh
Dec 19, 2017·Expert Opinion on Biological Therapy·Nathan HardcastleThais Federici
Nov 2, 2018·Science Translational Medicine·Florie BorelChristian Mueller
Mar 4, 2020·Expert Opinion on Therapeutic Targets·Elena AbatiStefania Corti
Oct 3, 2020·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Lin Wang, Lijuan Zhang
Nov 8, 2019·Advanced Healthcare Materials·Yusuke MorikawaTakeshi Kawano
Feb 7, 2019·Frontiers in Genetics·Zoe Butti, Shunmoogum A Patten
Dec 15, 2020·Biomaterials Science·João ConniotJoão Conde
Jan 7, 2021·Biomaterials Science·João ConniotJoão Conde
Dec 29, 2020·Neuroscience and Biobehavioral Reviews·Regine Sitruk-WareCesar V Borlongan
Feb 19, 2019·Molecular Therapy. Nucleic Acids·Raygene MartierPavlina Konstantinova
Feb 6, 2021·Acta Neuropathologica Communications·Pablo RozasDanilo B Medinas
Apr 2, 2021·The EMBO Journal·Maria Elena CicardiDavide Trotti
Jan 29, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Colin K W LimThomas Gaj
Nov 7, 2020·Current Gene Therapy·Md Sahab UddinGhulam Md Ashraf

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Methods Mentioned

BETA
transfection
protein assay
PCR
transgenic

Software Mentioned

ImageJ
Statistica

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