2020 ABN Fellowship
Validation of circulating exosomal diagnostic and prognostic biomarker candidates for Amyotrophic Lateral Sclerosis
There is currently no definitive diagnostic test for Amyotrophic Lateral Sclerosis (ALS), and patients often need to undergo multiple invasive investigations for their diagnosis. There is a typical diagnostic delay of 9-15 months from onset to diagnostic confirmation. Considering that the average survival from onset is 2-4 years and that efficacy of treatment is improved by early initiation, improved diagnostic speed would be beneficial to the treatment of ALS. There is an urgent need to identify disease-specific biomarkers that would be useful to diagnose patients and monitor effects of treatments.
Dr Duguez’s team have observed that vesicles released by muscle could be involved in the pathology of ALS: increased numbers of these microscopic structures are observed in the muscle of ALS patients, and muscle cells isolated from ALS patients accumulate and release them in large quantities. Importantly, these vesicles are neurotoxic - when added to cultures of motor neurons, the motor neurons die. By studying what is inside the vesicles, the team has identified 6 potential biomarkers.
In this project, we will test the potential of muscle vesicles and their contents as biomarkers to diagnose and to track disease progression through samples from current UK and French collaborations as well as patients recruited from Northern Ireland.
We will determine the presence of muscle vesicle biomarkers in blood serum samples. We hope to identify biomarkers that can be detected peripherally, leading to a non-invasive diagnostic/prognostic test for ALS within the next 5 years.
Publications
Serum Neurofilaments in Motor Neuron Disease and Their Utility in Differentiating ALS, PMA and PLS
Life (Basel). 2023 May 31;13(6):1301. doi: 10.3390/life13061301
2023
Genome-Wide Gene-Set Analysis Identifies Molecular Mechanisms Associated with ALS
International Journal of Molecular Sciences 2023 Feb 16;24(4):4021. doi: 10.3390/ijms24044021
2023
Risdiplam for the treatment of adults with spinal muscular atrophy: Experience of the Northern Ireland neuromuscular service
Muscle Nerve. 2023 Feb;67(2):157-161. doi: 10.1002/mus.27755
2023
Extracellular Vesicles in Amyotrophic Lateral Sclerosis
Life (Basel). 2022 Dec 31;13(1):121. doi: 10.3390/life13010121
2022
The Role of Sphingomyelin and Ceramide in Motor Neuron Diseases
Journal of Personalized Medicine 2022 Aug 30;12(9):1418. doi: 10.3390/jpm12091418
2022
Epidemiology and survival trends of motor neurone disease in Northern Ireland from 2015 to 2019
European Journal of Neurology 2022 Mar;29(3):707-714. doi: 10.1111/ene.15172
2022
A Systematic Review of Genotype-Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS
Journal of Personalized Medicine 2020 Jun 29;10(3):E58
2020