MetOxyRYR

BACKGROUND

RYR1-related myopathies are rare, neurodegenerative, genetically caused diseases for which there is currently no treatment. A novel mouse model has been developed that accurately replicates the symptoms observed in some patients by reducing RYR1 expression. This model is therefore particularly well-suited for the development and evaluation of new therapeutic strategies.

An increase in oxidative stress was observed in the muscles of the diseased mice. Treatment with antioxidants significantly slowed the loss of muscle strength. To better understand the molecular mechanisms responsible for this beneficial effect and to identify potential therapeutic targets, an in-depth analysis of the metabolic pathways affected by the treatment is planned, using metabolomics techniques (NMR).

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STUDENT CONTRIBUTION

The student will actively participate in the project by performing the following tasks:

1. Experimental follow-up: monitoring of cohorts of diseased mice, some treated with an antioxidant and others not, with regular assessments of motor performance and muscle strength over a 2-month period.
2. Sample collection: muscle and blood samples were collected at the end of the protocol for metabolic analysis.
3. Preparation and monitoring of analyses: preparation of samples for NMR metabolomics analyses (within the GIN) and monitoring of experiments.
4. Data analysis: processing and interpretation of metabolomics results.
5. Muscle histology: performing histological staining on muscle sections to correlate metabolic data with muscle structure.