Epigenetic small molecule screening identifies a new HDACi compound for ameliorating Duchenne muscular dystrophy

These data are the original data used to produce the figures, tables, and supplemental information for the manuscript "Epigenetic small molecule screening identifies a new HDACi compound for ameliorating Duchenne muscular dystrophy". In this study, our goal was to identify histone deacetylase inhibitors (HDACi), or other classes of epigenetic small molecules that are beneficial for DMD. Using an established animal model for DMD, the zebrafish dmd mutant strain sapje, we screened a library of over 800 epigenetic small molecules. Our screening identified a new HDACi, SR-4370, that ameliorated dmd mutant zebrafish skeletal muscle degeneration, as well as additional HDACi that have previously been shown to improve dmd zebrafish. We find that a single early treatment of HDACi can ameliorate the muscle phenotype and increase lifespan in dmd zebrafish. Furthermore, we find that HDACi treatments that improve dmd muscle also cause increased histone acetylation in zebrafish larvae. Our results add to the growing evidence that HDACi are promising candidates for treating DMD. Our study also provides further support for the effectiveness of small-molecule screening in dmd zebrafish.

本数据集为论文《表观遗传小分子筛选鉴定出可缓解杜氏肌营养不良的新型HDACi化合物》（"Epigenetic small molecule screening identifies a new HDACi compound for ameliorating Duchenne muscular dystrophy"）的配图、表格及补充信息所使用的原始实验数据。本研究旨在筛选可用于治疗杜氏肌营养不良（Duchenne muscular dystrophy, DMD）的组蛋白去乙酰化酶抑制剂（histone deacetylase inhibitors, HDACi）或其他类型的表观遗传小分子化合物；采用已成熟的DMD动物模型——斑马鱼（zebrafish）dmd突变株sapje，对包含800余种表观遗传小分子化合物的文库开展了筛选。本次筛选得到一种新型HDACi化合物SR-4370，其可缓解dmd突变斑马鱼的骨骼肌退行性病变；同时还筛选到此前已被证实可改善dmd斑马鱼表型的其他HDACi类化合物。研究发现，单次早期HDACi给药即可改善dmd突变斑马鱼的肌肉表型，并延长其生存寿命。此外，本研究还证实，可改善dmd斑马鱼肌肉表型的HDACi给药方案，能够提升斑马鱼幼体（zebrafish larvae）的组蛋白乙酰化水平。本研究结果进一步丰富了HDACi作为DMD潜在治疗候选药物的相关证据体系，同时也为基于dmd斑马鱼模型的小分子筛选策略的有效性提供了新的实验支撑。