2020 ABN Dr Gavin McClusky

Dr Gavin McCluskey

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.