Abstract
Amyotrophic lateral sclerosis (ALS) is a clinical subtype of motor neurone disease (MND), a fatal neurodegenerative disease involving the loss of both the upper and lower motor neurones from the motor cortex, brainstem, and spinal cord. Identifying specific disease biomarkers would help to not only improve diagnostic delay but also to classify disease subtypes, monitor response to therapeutic drugs and track disease progression. miRNAs are small non-coding RNA responsible for regulating gene expression and ultimately protein expression and have been used as biomarkers for many cancers and neurodegenerative disorders. Investigating the detection of miRNAs in cerebrospinal fluid (CSF), the fluid that bathes the central nervous system (CNS) is a prime target for identifying potential biomarkers for ALS. This is the first study to investigate the expression of miRNAs in the CSF of ALS patients using small RNA sequencing. We detected 11 differentially expressed miRNAs in the CSF of sporadic ALS (sALS) patients related to neural and glial activity. Additionally, miRNAs involved in glucose metabolism and the regulation of oxidative stress were also identified. Detecting the presence of potential CSF derived miRNA biomarkers in sALS could open up a whole new area of knowledge to help gain a better understanding of disease pathophysiology. Additionally, with further investigation, the tracking of CSF miRNA over the disease course could be used to follow the disease progression and monitor the effect of novel therapeutics that could be personalized to an individual disease phenotype.
Highlights
Amyotrophic lateral sclerosis (ALS) is the most common clinical subtype of motor neurone disease (MND), a fatal neurodegenerative disease involving the loss of both the upper and lower motor neurones from the motor cortex, brainstem, and spinal cord
No significant difference was identified in the levels of cel-miR-39 between the control and sporadic ALS (sALS) extracted cerebrospinal fluid (CSF) samples and all samples were viable for small RNA sequencing (Figure 2)
Our aim was to use small RNA sequencing to investigate differentially expressed miRNAs in the CSF of sALS patients compared with control subjects
Summary
Amyotrophic lateral sclerosis (ALS) is the most common clinical subtype of motor neurone disease (MND), a fatal neurodegenerative disease involving the loss of both the upper and lower motor neurones from the motor cortex, brainstem, and spinal cord. Identifying specific disease biomarkers would help to diagnose ALS and help to classify disease subtypes, monitor a patient’s response to therapeutic drugs and track disease progression. Our recently published paper shows the potential use of serum-based microRNAs (miRNAs) as biomarkers of ALS disease progression (Waller et al, 2017). Investigating miRNAs in cerebrospinal fluid (CSF), the fluid that bathes the central nervous system (CNS) is a prime target biosample for identifying potential biomarkers for ALS. Urine and saliva have been investigated as potential sources of disease biomarkers, miRNA biomarkers identified in the CSF may reflect changes in the degenerating cells, or could be markers reflecting pathophysiological changes in the brain, representing a more sensitive indicator of brain pathology than those present in blood or other biofluids
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