Dystrophinopathy and sarcoglycanopathies are incurable diseases caused by mutations in the genes encoding dystrophin or members of the dystrophin associated protein complex (DAPC). Restoration of the missing dystrophin or sarcoglycans via genetic approaches is complicated by the downsides of personalised medicines and immune responses against re-expressed proteins. Thus, the targeting of disease mechanisms downstream from the mutant protein has a strong translational potential. Acute muscle damage causes release of large quantities of ATP, which activates P2X7 purinoceptors, resulting in inflammation that clears dead tissues and triggers regeneration. However, in dystrophic muscles, loss of α-sarcoglycan ecto-ATPase activity further elevates extracellular ATP (eATP) levels, exacerbating the pathology. Moreover, seemingly compensatory P2X7 upregulation in dystrophic muscle cells, combined with high eATP leads to further damage. Accordingly, P2X7 blockade alleviated dystrophic damage in mouse models of both dystrophinopathy and sarcoglycanopathy. Existing P2X7 blockers could be re-purposed for the treatment of these highly debilitating diseases.

抗肌萎缩蛋白病和肌聚糖病是由编码抗肌萎缩蛋白或抗肌萎缩蛋白相关蛋白复合物 (DAPC) 成员的基因突变引起的无法治愈的疾病。通过以下方式恢复缺失的抗肌萎缩蛋白或肌聚糖由于个性化药物的缺点和针对重新表达的蛋白质的免疫反应，遗传方法变得复杂。因此，突变蛋白下游疾病机制的靶向具有很强的转化潜力。急性肌肉损伤导致释放大量 ATP，激活 P2X7 嘌呤受体，导致炎症清除死组织并触发再生。然而，在营养不良的肌肉中，α-肌聚糖胞外 ATP 酶活性的丧失会进一步提高细胞外 ATP (eATP) 水平，从而加剧病理。此外，营养不良的肌肉细胞中看似补偿性的 P2X7 上调与高 eATP 相结合会导致进一步的损伤。因此，P2X7 阻断减轻了肌营养不良症和肌聚糖病小鼠模型的营养不良性损伤。