PDF(Pubmed)
Abstract：
Genetic mitochondrial diseases represent a significant challenge to human health. These diseases are extraordinarily heterogeneous in clinical presentation and genetic origin, and often involve multi-system disease with severe progressive symptoms. Mitochondrial diseases represent the most common cause of inherited metabolic disorders and one of the most common causes of inherited neurologic diseases, yet no proven therapeutic strategies yet exist. The basic cell and molecular mechanisms underlying the pathogenesis of mitochondrial diseases have not been resolved, hampering efforts to develop therapeutic agents.
In recent pre-clinical work, we have shown that pharmacologic agents targeting the immune system can prevent disease in the Ndufs4(KO) model of Leigh syndrome, indicating that the immune system plays a causal role in the pathogenesis of at least this form of mitochondrial disease. Intriguingly, a number of case reports have indicated that immune-targeting therapeutics may be beneficial in the setting of genetic mitochondrial disease. Here, we summarize clinical and pre-clinical evidence suggesting a key role for the immune system in mediating the pathogenesis of at least some forms of genetic mitochondrial disease.
Significant clinical and pre-clinical evidence indicates a key role for the immune system as a significant in the pathogenesis of at least some forms of genetic mitochondrial disease.
In recent pre-clinical work, we have shown that pharmacologic agents targeting the immune system can prevent disease in the Ndufs4(KO) model of Leigh syndrome, indicating that the immune system plays a causal role in the pathogenesis of at least this form of mitochondrial disease. Intriguingly, a number of case reports have indicated that immune-targeting therapeutics may be beneficial in the setting of genetic mitochondrial disease. Here, we summarize clinical and pre-clinical evidence suggesting a key role for the immune system in mediating the pathogenesis of at least some forms of genetic mitochondrial disease.
Significant clinical and pre-clinical evidence indicates a key role for the immune system as a significant in the pathogenesis of at least some forms of genetic mitochondrial disease.
摘要：
遗传性线粒体疾病是对人类健康的重大挑战。这些疾病在临床表现和遗传起源方面异常异质性，并且通常涉及具有严重进行性症状的多系统疾病。线粒体疾病是遗传性代谢紊乱的最常见原因，也是遗传性神经系统疾病的最常见原因之一。然而，目前还没有成熟的治疗策略。线粒体疾病发病机制的基本细胞和分子机制尚未得到解决，阻碍开发治疗剂的努力。
在最近的临床前工作中，我们已经证明，靶向免疫系统的药物可以预防疾病的Ndufs4（KO）Leigh综合征的模型，表明免疫系统在至少这种形式的线粒体疾病的发病机理中起着因果作用。有趣的是，大量病例报告表明,免疫靶向治疗可能对遗传性线粒体疾病有益.这里,我们总结了临床和临床前证据，这些证据表明免疫系统在介导至少某些形式的遗传性线粒体疾病的发病机制中起关键作用。
重要的临床和临床前证据表明免疫系统在至少某些形式的遗传性线粒体疾病的发病机理中起着重要作用。
在最近的临床前工作中，我们已经证明，靶向免疫系统的药物可以预防疾病的Ndufs4（KO）Leigh综合征的模型，表明免疫系统在至少这种形式的线粒体疾病的发病机理中起着因果作用。有趣的是，大量病例报告表明,免疫靶向治疗可能对遗传性线粒体疾病有益.这里,我们总结了临床和临床前证据，这些证据表明免疫系统在介导至少某些形式的遗传性线粒体疾病的发病机制中起关键作用。
重要的临床和临床前证据表明免疫系统在至少某些形式的遗传性线粒体疾病的发病机理中起着重要作用。
