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Urinary biomarkers for amyotrophic lateral sclerosis: candidates, opportunities and considerations

Journal

BRAIN COMMUNICATIONS
Volume 5, Issue 6, Pages -

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/braincomms/fcad287

Keywords

ALS; urine; biomarker; proteins; metabolites

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Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by degeneration of upper and lower motor neurons. Finding fluid-based biomarkers that reflect the pathological processes is crucial for evaluating treatment efficacy, and urine may be a rich source of candidate biomarkers.
Amyotrophic lateral sclerosis is a relentless neurodegenerative disease that is mostly fatal within 3-5 years and is diagnosed on evidence of progressive upper and lower motor neuron degeneration. Around 15% of those with amyotrophic lateral sclerosis also have frontotemporal degeneration, and gene mutations account for similar to 10%. Amyotrophic lateral sclerosis is a variable heterogeneous disease, and it is becoming increasingly clear that numerous different disease processes culminate in the final degeneration of motor neurons. There is a profound need to clearly articulate and measure pathological process that occurs. Such information is needed to tailor treatments to individuals with amyotrophic lateral sclerosis according to an individual's pathological fingerprint. For new candidate therapies, there is also a need for methods to select patients according to expected treatment outcomes and measure the success, or not, of treatments. Biomarkers are essential tools to fulfil these needs, and urine is a rich source for candidate biofluid biomarkers. This review will describe promising candidate urinary biomarkers of amyotrophic lateral sclerosis and other possible urinary candidates in future areas of investigation as well as the limitations of urinary biomarkers. Finding objective fluid-based biomarkers for amyotrophic lateral sclerosis that reflect the pathological processes occurring in a phenotypically heterogeneous disease is essential for assessing if treatments are working or not. This requires evaluating alternate non-invasive biofluids such as urine, with caveats such as standardizing collection, processing and validating candidates. Graphical Abstract

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