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Project
TREAT-SARCO: Development of a novel gene therapy strategy for sarcoglycan deficiency (FWOAL973)
Limb Girdle Muscular Dystrophy Type 2E (LGMD2E) is caused by mutations in the beta-sarcoglycan gene resulting in progressive weakness and wasting of the skeletal muscles, diaphragm and heart. This causes loss of mobility in early childhood and death in young adults due to cardiopulmonary failure. There is currently no effective treatment available, which underscores the high unmet medical
need. Gene therapy provides new opportunities to treat LGMD2E. Nevertheless, achieving safe, robust and widespread expression of therapeutic genes in the heart, skeletal muscles and diaphragm remains challenging. It is therefore imperative to further improve the efficacy and safety of heart, diaphragm and skeletal muscle-directed gene therapy for LGMD2E. More robust gene therapy vectors will therefore be developed that allow for sustainable and widespread therapeutic gene expression. This project takes advantage of extensive preliminary data that supports the use of genome-wide data-mining that led to the identification of novel transcriptional cis- regulatory modules (CRM). These novel and robust CRM elements substantially increased expression of the therapeutic genes after gene therapy. The ultimate goal is to simultaneously achieve robust
amelioration of heart, skeletal muscle and diaphragm dysfunction in a clinically-relevant LGMD2E disease model with potential broad implications for the field
need. Gene therapy provides new opportunities to treat LGMD2E. Nevertheless, achieving safe, robust and widespread expression of therapeutic genes in the heart, skeletal muscles and diaphragm remains challenging. It is therefore imperative to further improve the efficacy and safety of heart, diaphragm and skeletal muscle-directed gene therapy for LGMD2E. More robust gene therapy vectors will therefore be developed that allow for sustainable and widespread therapeutic gene expression. This project takes advantage of extensive preliminary data that supports the use of genome-wide data-mining that led to the identification of novel transcriptional cis- regulatory modules (CRM). These novel and robust CRM elements substantially increased expression of the therapeutic genes after gene therapy. The ultimate goal is to simultaneously achieve robust
amelioration of heart, skeletal muscle and diaphragm dysfunction in a clinically-relevant LGMD2E disease model with potential broad implications for the field
Date:1 Jan 2020 → 31 Dec 2023
Keywords:cardiovascular sciences, gene therapy, musculo-skeletal systems
Disciplines:Cell physiology, Genetics, Molecular and cell biology not elsewhere classified, Molecular physiology