A5066256578- Muscle Physiology and Disorders
- RNA Research and Splicing
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- Virus-based gene therapy research
- MicroRNA in disease regulation
- Genetic Neurodegenerative Diseases
- 3D Printing in Biomedical Research
- CAR-T cell therapy research
- GDF15 and Related Biomarkers
- Forensic Toxicology and Drug Analysis
- Autophagy in Disease and Therapy
- Tissue Engineering and Regenerative Medicine
- Calcium signaling and nucleotide metabolism
- Conducting polymers and applications
- Cardiomyopathy and Myosin Studies
- Mitochondrial Function and Pathology
- Viral Infections and Immunology Research
- Cerebrovascular and Carotid Artery Diseases
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- Cardiovascular Health and Disease Prevention
- Medical Research and Treatments
- Cannabis and Cannabinoid Research
- Lipid metabolism and disorders
Genethon (France)
2019-2025
Université Paris-Saclay
2020-2024
Inserm
2020-2024
Integrated Genetic Approaches in Therapeutic Discovery for Rare Diseases
2020-2024
Bangur Institute of Neurosciences
2008
Duchenne Muscular Dystrophy (DMD), a muscle degenerative disease affecting young boys, arises from the loss of dystrophin. Current gene therapy approaches aim to restore shortened form dystrophin (microdystrophin) via Adeno-Associated Vector (AAV) delivery, but clinical studies show limited efficacy, emphasizing need for improved strategies such as combined therapies. In this study, we identified lysosomal perturbations in myofibers DMD patients and animal models, an overlooked mechanism...
<title>Abstract</title> Current gene therapy approaches for Duchenne muscular dystrophy (DMD) using AAV-mediated delivery of microdystrophin (µDys) have shown limited efficacy in patients, contrasting with the favorable outcomes observed animal models. This discrepancy is partly due to lack models that replicate key pathogenic features associated severity human disease, such as fibrosis and muscle dysfunction. To tackle translational gap, we develop a disease model recapitulates these...
Abstract Duchenne Muscular Dystrophy (DMD) is a lethal muscle disorder, caused by mutations in the DMD gene and affects approximately 1:5000–6000 male births. In this report, we identified dysregulation of members Dlk1-Dio3 miRNA cluster biopsies GRMD dog model. Of these, selected miR-379 for detailed investigation because its expression high muscle, known to be responsive glucocorticoid, class anti-inflammatory drugs commonly used patients. Bioinformatics analysis predicts that targets...
Duchenne muscular dystrophy (DMD) is a severe muscle disease caused by impaired expression of dystrophin. Whereas mitochondrial dysfunction thought to play an important role in DMD, the mechanism this remains be clarified. Here we demonstrate that DMD and other dystrophies, large number Dlk1-Dio3 clustered miRNAs (DD-miRNAs) are coordinately up-regulated regenerating myofibers serum. To characterize biological effect dysregulation, 14 DD-miRNAs were simultaneously overexpressed vivo mouse...
Duchenne muscular dystrophy (DMD) is the most common and cureless muscle pediatric genetic disease, which caused by lack or drastically reduced expression of dystrophin. Experimental therapeutic approaches for DMD have been mainly focused in recent years on attempts to restore While significant progress was achieved, benefit treated patients still unsatisfactory. Efficiency gene therapy hampered not only incompletely resolved technical issues, but likely also due progressive nature DMD. It...
We recently identified a signaling pathway that links the upregulation of miR-379 with mitochondrial response in dystrophic muscle. In present commentary, we explain significance this may have dysfunction Duchenne muscular dystrophy (DMD). serum and muscles DMD animal models patients. found is one very few miRNAs whose expression was normalized patients treated glucocorticoid. EIF4G2 as target, which promote oxidative phosphorylation (OxPhos) skeletal enriched fibers, ATP synthase subunit...
Duchenne Muscular Dystrophy (DMD) is a pediatric disorder characterized by progressive muscle degeneration and premature death, with no cure at the moment. The currently most promising therapeutic avenue based on gene replacement mediated adeno-associated viruses (AAVs) using shortened, but still functional, version of Dystrophin, known as microdystrophin (µDys), to fit AAV capacity. limited improvements observed in clinical trials suggest sub-optimal performance µDys human context, that...
Duchenne Muscular Dystrophy (DMD) is a pediatric disorder characterized by progressive muscle degeneration and premature death, has no current cure. The current, most promising therapeutic avenue based on gene replacement mediated adeno-associated viruses (AAVs) using shortened, but still functional, version of dystrophin, known as micro-dystrophin (µDys), to fit AAV capacity. limited improvements observed in clinical trials suggest sub-optimal performance µDys the human context that could...
Abstract Current adeno-associated virus (AAV) gene therapy using nature-derived AAVs is limited by non-optimal tissue targeting. In the treatment of muscular diseases (MD), high doses are therefore often required, but can lead to severe adverse effects. To lower doses, we rationally designed an AAV that specifically targets skeletal muscle. We employed a novel computational design integrated binding motifs integrin alpha V beta 6 (αVβ6) into liver-detargeting capsid backbone target human...
It is now well-established that microRNA dysregulation a hallmark of human diseases, and aberrant expression miRNA not randomly associated with pathologies but plays causal role in the pathological process. Investigations molecular mechanism links to pathophysiology can therefore further understanding diseases. The biological effect thought be mediated principally by target genes. Consequently, genes dysregulated serve as proxy for interpretation dysregulation, which performed gene pathway...
Abstract Background Duchenne Muscular Dystrophy (DMD) is a lethal muscle disease detected in approximately 1:5000 male births. DMD caused by mutations the gene, encoding critical protein that link cytoskeleton and extracellular matrix skeletal cardiac muscles. The primary consequence of disrupted between myofiber actin thought to involve sarcolemma destabilization, perturbation Ca +2 homeostasis, activation proteases, mitochondrial damage tissue degeneration. A recently emphasized secondary...
SUMMARY Current gene therapy approaches for Duchenne muscular dystrophy (DMD) using AAV-mediated delivery of microdystrophin (µDys) have shown limited efficacy in patients, contrasting with the favorable outcomes observed animal models. This discrepancy is partly due to lack models that replicate key pathogenic features associated severity human disease, such as fibrosis and muscle dysfunction. To tackle translational gap, we develop a disease model recapitulates these critical hallmarks DMD...
Abstract Background Duchenne Muscular Dystrophy (DMD) is a severe muscle disease caused by impaired expression of dystrophin. While mitochondrial dysfunction thought to play an important role in DMD, the mechanism this remains be clarified. We recently identified DMD and other muscular dystrophies upregulation large number Dlk1-Dio3 clustered miRNAs (DD-miRNAs), both serum. The objective present study was define biological functions DD-miRNAs skeletal muscle, particularly context dystrophy....