The Target ALS Human Postmortem Tissue Core facilitated groundbreaking work led by Moses Leavens from the McLaughlin Research Institute for Biomedical Sciences. In a paper recently published by Dr. Leavens and his collaborators from Washington University, University of Montana, NIAID, and the University of British Columbia in Acta Neuropathologica, the group reports that SOD1 aggregates can be detected in the postmortem tissue of ALS patients without an ALS-causing SOD1 gene mutation.
The cross-institutional group of researchers used a technique called real-time quaking-induced conversion (RT-QuIC), a seed amplification assay (SAA) that allows for the detection of prions and prion-like proteins in biosamples. SAAs have been used successfully to detect protein aggregates or as a diagnostic biomarker for illnesses like Parkinson’s disease, Alzheimer’s disease, and Creutzfeldt-Jakob disease, but have not yet been applied clinically to ALS. Dr. Leavens’ group aimed to use an RT-QuIC assay to detect SOD1 aggregates in postmortem tissue from individuals diagnosed with ALS acquired from the Target ALS Human Postmortem Tissue Core. Surprisingly, their RT-QuIC assay indicated that there were prion-like aggregates of SOD1 protein in the spinal cord and motor cortex not only in individuals with ALS caused by mutations in the SOD1 gene but also in individuals diagnosed with sporadic ALS (sALS, no inherited causal gene mutation) and individuals with ALS caused by a hexanucleotide repeat expansion in the C9orf72 gene. Typically, people with sALS and C9orf72 familial ALS are thought to have aggregates of TDP-43 protein, rather than SOD1. This result from Dr. Leavens’ team suggests that diagnostic biomarkers developed for specific forms of familial ALS may also provide benefits for individuals with sALS, which comprises 90% of ALS cases and has no currently available disease-modifying therapeutics or diagnostic tools. His lab is already advancing this work to the next stage – validation of SOD1 RT-QuIC assay in human biofluids from people living with ALS obtained from the Target ALS Longitudinal Biofluid Core.
Target ALS is thrilled that our Human Postmortem Tissue Core, the largest ALS postmortem biobank globally, was utilized to perform this exciting work which provides hope for future diagnosis and treatment for all forms of ALS. Target ALS is directly supporting additional work to understand protein aggregation biology and develop SAAs as diagnostic tools for ALS via two of our funded early-in-career researchers, New Academic Investigator Javier Oroz and Neurology Resident Sarah Smith. We are also directly supporting additional work that aims to apply breakthroughs in familial ALS to all forms of ALS via a newly funded Basic Biology consortium led by Steven Altschuler at UCSF. Target ALS also supports work from a consortium including Gianluigi Zanusso at the University of Verona whose lab reported the identification of patients diagnosed with frontotemporal dementia using RT-QuIC to detect aggregated TDP-43 protein in nasal swabs.
As part of our commitment to break down barriers to accelerate ALS research, Target ALS Research Cores and funding opportunities are available to ALS researchers from academia and industry worldwide. We provide all Core resources at low or no cost and never request IP rights. To use postmortem tissue from the Target ALS Human Postmortem Tissue Core in your own research or apply for a research grant from Target ALS, visit our website.
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