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Moderate-level resistance exercise significantly improved the Sickness Impact Profile ALS-19 and muscle transcriptome of the early-stage ALS patients.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) patients lose motor and neuromuscular function but lack effective treatments. The objective of this study was to evaluate the effect of moderate-level exercise on ALS scores, neuromuscular function, and transcriptome in ALS patients. Methods: A pilot open-label, non-randomized clinical trial was conducted in seven individuals with early-stage ALS. Participants were given three months of moderate-level home-based resistance exercise focusing on the quadriceps muscles. Before and after the exercise program, participants were evaluated by quantifiable outcome measures using bilateral quadriceps strength with manual muscle testing and handheld dynamometers and functional outcome measures using five times sit-to-stand and Timed-Up-and-Go. In addition, changes in the transcriptome and mitochondrial respiration of exercised muscles were compared before and after the exercise. Results: The exercise program significantly improved the Sickness Impact Profile ALS-19 (SIP/ALS-19) and did not cause serious adverse events to the patients. ALSFRS-R, quantifiable outcome measures, functional outcome measures, and muscle respiration values did not change by the exercise program. Transcriptome analysis revealed that exercise reverted the expression level of genes decreased in ALS, including PVALB. Conclusions: Three months of moderate-level resistance exercise is not detrimental for the patients and may have a positive effect on patients’ QOL.

ORGANISM(S): Homo sapiens

PROVIDER: GSE250455 | GEO | 2024/09/25

REPOSITORIES: GEO

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Project description:Background Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, muscle atrophy and paralysis. To date, multiple panels of biomarkers have been described in ALS patients and murine models. Nevertheless, none of them has sufficient specificity and thus the molecular signature for ALS prognosis and progression remains to be fully elucidated. Circulating microRNAs (miRNAs) are highly stable molecules that are recently used as promising biomarkers for many types of human cancer and muscle disorders. Here we overcome this limitation through a longitudinal study, analyzing serum levels of circulating miRNAs in ALS patients during the progression of the pathology. Method We performed next-generation sequencing (NGS) analysis and absolute RT quantification of serum samples of 27 ALS patients and 11 healthy control; among them 13 ALS patients were studied every three months till the end of the disease. Results We demonstrated that miR-151a-3p, miR-206 and miR-199a-3p are significantly expressed at the mild, moderate and severe stages of ALS pathology, whereas the expression levels of miR-133a and miR-199a-5p remained low during the whole study and retain diagnostic significance in the moderate and severe stages (miR-133a) and in mild and terminal stages (miR-199a-5p) of the disease. Moreover, we analysed the miRNAs serum levels during the progression of the disease in each patient and we demonstrated that high levels of miR-206, miR-133a, miR-151a-5p, miR-151a-3p can predict a slower clinical decline of patient functionality suggesting that these miRNAs represent good potential prognostic markers for ALS disease. Conclusion This study is the first to perform a longitudinal absolute quantification of circulating miRNAs during ALS disease. We highlighted putative biomarkers for diagnosis, prognosis and disease stage identification of ALS patients providing cut-off threshold for most of the miRNAs analyzed. In addition, our results define a molecular signature of ALS phenotypes that could help to define appropriate enrollments of patients in clinical trials.