Journal article
Evidence for disrupted copper availability in human spinal cord supports CuII(atsm) as a treatment option for sporadic cases of ALS
JBW Hilton, K Kysenius, JR Liddell, SW Mercer, B Paul, JS Beckman, CA McLean, AR White, PS Donnelly, AI Bush, DJ Hare, BR Roberts, PJ Crouch
Scientific Reports | Published : 2024
Abstract
The copper compound CuII(atsm) has progressed to phase 2/3 testing for treatment of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). CuII(atsm) is neuroprotective in mutant SOD1 mouse models of ALS where its activity is ascribed in part to improving availability of essential copper. However, SOD1 mutations cause only ~ 2% of ALS cases and therapeutic relevance of copper availability in sporadic ALS is unresolved. Herein we assessed spinal cord tissue from human cases of sporadic ALS for copper-related changes. We found that when compared to control cases the natural distribution of spinal cord copper was disrupted in sporadic ALS. A standout feature was decreased copper lev..
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Funding Acknowledgements
Human tissue samples donated with informed consent were obtained from the Victorian Brain Bank (Florey Institute of Neuroscience and Mental Health, the University of Melbourne, Australia) with assistance from Ms Fairlie Hinton and Mr Geoff Pavey, and the MS Society Tissue Bank (Wolfson Neuroscience Laboratories, Imperial College London, United Kingdom) with assistance from Dr Djordie Gveric. Total copper levels in human spinal cord were measured at the Biometals Facility at the Florey Institute of Neuroscience and Mental Health, the University of Melbourne, by Ms Irene Volitakis. Fig. 3a was created using Biorender.com. This research was supported by funding from the Motor Neurone Disease Research Institute of Australia (Beryl Bayley Fellowship to JBWH; Betty Laidlaw MND Research Project to PJC, BRR, DJH, ARW, JSB, PSD and CAM; Jenny Barr Smith MND Research Project to PJC, AIB, BRR, JSB and CAM), Perpetual IMPACT Philanthropy (Margaret Dawn Marks Charitable Trust), and the University of Melbourne.