Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressing neurodegenerative disease whereby 50% of cases die within 3 years. Diagnosis involves a clinical examination with a questionnaire-based scale (ALSFRS-R) and a nerve conduction test. The process from symptom presentation to diagnosis can take an average of 12 months and there is a critical need for an objective and economical test to detect ALS.

We have initiated an innovative project, together with collaborators at the University of California, San Francisco (USA, CI: Zaitlen) to investigate cell-free DNA (cfDNA) in ALS. CfDNA is DNA that enters the bloodstream when cells die. It can be measured economically and is being actively used in the prenatal diagnostic and cancer fields to provide direction about treatment and health. Recent work has now demonstrated that cfDNA (detectable when there is cell death) can be mapped back to its tissue-of-origin that is relevant to known disease processes. In preliminary studies, we have found that ALS cases have greater amounts of cfDNA than controls to suggest an increase in cell death is occurring. Now we propose to collect ALS disease mimics and carry out qualitative analysis to help identify an ALS specific cfDNA profile. We hypothesize that the sequencing of cfDNA in ALS cases and controls will show a distinct profile such as neuron and muscle cell death, and this signal could address the ALS biomarker dilemma that currently exists.

Our primary objective is to translate this research into a clinical tool for diagnosis and tracking in ALS. Our project proposal will allow us to continue to test if cfDNA is viable and robust to detect ALS in a larger number of individuals. Identifying if cfDNA is correlated with the primary mechanism of disease and disease progression could offer a minimally invasive, efficient and economical means for diagnosis, disease monitoring, and assessment of response to therapeutic treatment – none of which currently exist for ALS patients.

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