申请人:Alnylam Pharmaceuticals, Inc.
公开号:EP3960860A2
公开(公告)日:2022-03-02
The present invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the ketohexokinase (KHK) gene, and methods of using such RNAi agents to inhibit expression of KHK and methods of treating subjects having a KHK-associated disorder, e.g., liver disease (e.g., fatty liver, steatohepatitis), dyslipidemia (e.g., hyperlipidemia, high LDL cholesterol, low HDL cholesterol, hypertriglyceridemia, postprandial hypertriglyceridemia), disorders of glycemic control (e.g., insulin resistance, diabetes), cardiovascular disease (e.g., hypertension, endothelial cell dysfunction), kidney disease (e.g., acute kidney disorder, tubular dysfunction, proinflammatory changes to the proximal tubules), metabolic syndrome, adipocyte dysfunction, visceral adipose deposition, obesity, hyperuricemia, gout, eating disorders, and excessive sugar craving.
本发明涉及靶向酮合酶(KHK)基因的RNAi制剂,例如双链RNAi制剂,以及使用这种RNAi制剂抑制KHK表达的方法和治疗患有KHK相关疾病的受试者的方法,例如、肝脏疾病(如脂肪肝、脂肪性肝炎)、血脂异常(如高脂血症、高低密度脂蛋白胆固醇、低高密度脂蛋白胆固醇、高甘油三酯血症、餐后高甘油三酯血症)、血糖控制障碍(如胰岛素抵抗、糖尿病)、胰岛素抵抗、糖尿病)、心血管疾病(如高血压、血管内皮细胞功能障碍)、肾脏疾病(如急性肾功能紊乱、肾小管功能障碍、近端肾小管的促炎性变化)、代谢综合征、脂肪细胞功能障碍、内脏脂肪沉积、肥胖、高尿酸血症、痛风、饮食失调和过度嗜糖。