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Financement de l’UE (196 708 €) : Recâblage avec signalisation biaisée pour remplacer les défauts de la voie oxydative pour le traitement de la myopathie liée à SEPN1 Hor23/04/2020 Programme de recherche et d'innovation de l'UE « Horizon »
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Texte
Recâblage avec signalisation biaisée pour remplacer les défauts de la voie oxydative pour le traitement de la myopathie liée à SEPN1
SEPN1-related myopathy (SEPN1-RM) is a rare, untreatable debilitating congenital myopathy in which SEPN1 mutations impair the antioxidant system, ER stress protection and mitochondrial oxidative function. These altered cellular processes ultimately lead to a significant loss of bioenergetic production and abrogate muscle cellular functions. SEPN1-RM patients experience potentially-lethal respiratory failure and major life burden due to loss of mobility. Currently, there are no high-throughput or appropriate preclinical models to facilitate identification of disease-modifying drugs; this has hampered efforts in devising therapeutic strategies. To overcome these bottlenecks, I aim to use patient-derived cells to establish (1) high-throughput measureable readouts of metabolism, facilitating repurposed drug screen for SEPN1-RM; (2) an original treatment strategy by exploiting potential biased signalings, which bypass SEPN1 defects to restore cellular bioenergetics. I will capitalize on (1) the availability of SEPN1-RM biopsies, (2) host lab expertise for handling and culturing primary SEPN1-RM cells and (3) my experience in muscle biology and innovative tools for analysing metabolic/signalling pathways. I aim to implement transcriptomic analyses by using next-generation RNA-seq, optogenetic based sensors to quantify metabolic activity, real-time clonal analysis of cell fate with dynamic fluorescent time-lapse microscopy and multi-dimensional assessment of intracellular activities at single-cell level via CYTOF technology. This study will not only facilitate the establishment of SEPN1-RM biomarkers and novel therapeutic studies, it will also provide a model paradigm for analysing and treating other inherited or acquired myopathies sharing an underlying bioenergetic deficiency, including sarcopenia and cancer cachexia.
| Universite Paris Cite | 196 708 € |
https://cordis.europa.eu/project/id/897735
Cette annonce se réfère à une date antérieure et ne reflète pas nécessairement l’état actuel. L’état actuel est présenté à la page suivante : Universite Paris Cite, Paris.