2024
Newly developed oral bioavailable EHMT2 inhibitor as a potential epigenetic therapy for Prader-Willi syndrome
Wang S, Xiong Y, Jang M, Park K, Donahue M, Velez J, Jin J, Jiang Y. Newly developed oral bioavailable EHMT2 inhibitor as a potential epigenetic therapy for Prader-Willi syndrome. Molecular Therapy 2024, 32: 2662-2675. PMID: 38796700, DOI: 10.1016/j.ymthe.2024.05.034.Peer-Reviewed Original ResearchPrader-Willi syndromeEpigenetic therapyMouse modelChromosome 15q11-q13 regionPWS mouse modelFirst-in-class inhibitorEfficacy of oral administrationPoor oral bioavailabilityPotential epigenetic therapiesReduction of H3K9me2Paternally expressed genesOral bioavailabilityIntraperitoneal routeOral administrationPerinatal lethalityTherapeutic benefitBrain penetrationMolecular efficacyPatient fibroblastsEpigenetic modulationGenomic disordersMaternal chromosomeBrain permeabilityLiver tissueCandidate genes
2019
Epigenetic therapy of Prader–Willi syndrome
Kim Y, Wang SE, Jiang YH. Epigenetic therapy of Prader–Willi syndrome. Translational Research 2019, 208: 105-118. PMID: 30904443, PMCID: PMC6527448, DOI: 10.1016/j.trsl.2019.02.012.Peer-Reviewed Original ResearchConceptsPWS mouse modelEpigenetic-based therapiesMaternal chromosomesImprinted gene regulationEHMT2/G9aLysine 9 methyltransferasePatient-derived fibroblastsPrader-Willi syndromeGene regulationMethyltransferase SETDB1Epigenetic mechanismsSmall molecule librariesPWS genesHigh-content screeningSame genePerinatal lethalityEpigenetic therapyFusion proteinMolecular mechanismsG9a inhibitorChromosomesSNORD116 clusterGenesMolecular defectsPatient iPSC