Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism
Cohen J, Huang S, Koczwara K, Woods K, Ho V, Woodman K, Arbiser J, Daman K, Lek M, Emerson C, DeSimone A. Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism. Cell Death & Disease 2023, 14: 749. PMID: 37973788, PMCID: PMC10654915, DOI: 10.1038/s41419-023-06257-2.Peer-Reviewed Original ResearchConceptsMTOR-independent mechanismsFacioscapulohumeral muscular dystrophyDUX4 transcriptsDUX4 activityMultiple signal transduction pathwaysSignal transduction pathwaysTherapeutic developmentDUX4 proteinDUX4 expressionTransduction pathwaysPolyadenylation sitesChromosome 4DUX4 geneMechanisms of toxicityAutophagy pathwayExpression of ULK1DUX4Cellular autophagyCell deathRelevant pathwaysMuscular dystrophyMolecular methodsPathwaySkeletal muscleTranscriptsP299 Over-expression of FKRP in heart induces myocarditis and dilated cardiomyopathy in LGMD2I/R9 mice
Huang S, Ma K, Cohen J, Ho V, Xu J, Gauthier L, O'Connor C, Ge L, Woodman K, Lek M. P299 Over-expression of FKRP in heart induces myocarditis and dilated cardiomyopathy in LGMD2I/R9 mice. Neuromuscular Disorders 2023, 33: s118. DOI: 10.1016/j.nmd.2023.07.209.Peer-Reviewed Original ResearchGene replacement therapyReplacement therapySkeletal muscleFKRP geneLeft ventricular cavity sizeEvidence of myocarditisHigh expressionLow ejection fractionVentricular cavity sizeAutosomal recessive disorderCardiac involvementEjection fractionInflammatory infiltrationCardiac statusCardiac outputFatal cardiotoxicityFatal myocarditisDosed miceInclusion criteriaHeart sectionsMouse modelDystrophic miceDystrophic pathologyFKRP mutationsPatients