Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK.
Neurobiol Dis. 2009 Nov;36(2):242-51. doi: 10.1016/j.nbd.2009.07.010. Epub 2009 Jul 24.
Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal disorder characterized by sphingolipid and cholesterol storage in the late endocytic system. In common with other neurodegenerative diseases, activation of the innate immune system occurs in the brain resulting in neuro-inflammation. Targeting inflammation in the brain therefore represents a potential clinical intervention strategy that aims to slow the rate of disease progression and improve quality of life. We evaluated non-steroidal anti-inflammatory drugs (NSAIDs) and an anti-oxidant to determine whether these agents are disease modifying in an acute mouse model of NPC1. NSAIDs significantly prolonged the lifespan of NPC1 mice and slowed the onset of clinical signs. However, anti-oxidant therapy was of no significant benefit. Combining NSAID therapy with substrate reduction therapy (SRT) resulted in additive benefit. These data suggest that anti-inflammatory therapy may be a useful adjunctive treatment in the clinical management of NPC1, alone or combined with SRT.
尼曼-匹克病 C1 型（NPC1）是一种神经退行性溶酶体疾病，其特征是晚期内吞系统中鞘脂和胆固醇的储存。与其他神经退行性疾病一样，中枢神经系统中的固有免疫系统被激活，导致神经炎症。因此，靶向大脑中的炎症代表了一种潜在的临床干预策略，旨在减缓疾病进展速度并提高生活质量。我们评估了非甾体抗炎药（NSAIDs）和抗氧化剂，以确定这些药物是否在 NPC1 的急性小鼠模型中具有疾病修饰作用。NSAIDs 显著延长了 NPC1 小鼠的寿命，并减缓了临床症状的出现。然而，抗氧化剂治疗没有显著益处。将 NSAID 治疗与底物还原治疗（SRT）相结合可带来额外益处。这些数据表明，抗炎治疗可能是 NPC1 临床治疗的有用辅助手段，可单独使用或与 SRT 联合使用。
