Journal article

Cu-II(atsm) improves the neurological phenotype and survival of SOD1(G93A) mice and selectively increases enzymatically active SOD1 in the spinal cord

James B Hilton, Stephen W Mercer, Nastasia KH Lim, Noel G Faux, Gojko Buncic, Joseph S Beckman, Blaine R Roberts, Paul S Donnelly, Anthony R White, Peter J Crouch

SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2017

Abstract

Ubiquitous expression of mutant Cu/Zn-superoxide dismutase (SOD1) selectively affects motor neurons in the central nervous system (CNS), causing the adult-onset degenerative disease amyotrophic lateral sclerosis (ALS). The CNS-specific impact of ubiquitous mutant SOD1 expression is recapitulated in transgenic mouse models of the disease. Here we present outcomes for the metallo-complex CuII(atsm) tested for therapeutic efficacy in mice expressing SOD1G93A on a mixed genetic background. Oral administration of CuII(atsm) delayed the onset of neurological symptoms, improved locomotive capacity and extended overall survival. Although the ALS-like phenotype of SOD1G93A mice is instigated by expre..

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Grants

Awarded by National Health and Medical Research Council


Awarded by DoD Congressionally Directed Medical Research Program


Awarded by Ice Bucket


Funding Acknowledgements

This work was funded by the National Health and Medical Research Council (Project Grant 1061550 to PJC and PSD; Career Development Fellowship 1084927 to PJC) the University of Melbourne (Research Grant Support Scheme to PJC), and the Motor Neurone Disease Research Institute of Australia (Zo-ee MND Research Grant to PJC and BRR). Part of this work was also supported by funding from the DoD Congressionally Directed Medical Research Program (AL140108 to JSB) and by Ice Bucket donations made to the ALSA (Research Award ALSA 320 to JSB). JBH was recipient of the Australian Postgraduate Award and the Nancy Frances Curry Scholarship. All SOD1<SUP>G93A</SUP> mice and non-transgenic littermates in this study were from The Jackson Laboratory and generously provided by Prize4Life. All ICP-MS analyses were performed by Ms Irene Volitakis at the Biometals Facility, Florey Institute of Neurosciences and Mental Health. Assoc. Prof. Peter Crack kindly provided the Iba-1 antibody.