原发性高草酸尿症的基因治疗进展

Advances in the gene therapy of primary hyperoxaluria

原发性高草酸尿症(PH)是一种罕见的常染色体隐性遗传病,以肝脏乙醛酸代谢相关酶异常所致的草酸钙肾结石和肾钙质沉着为主要临床特征。目前,PH治疗方式较少,药物和肝移植等传统治疗方法虽能延缓疾病进展,减轻患者症状,但效果有限。近年来,生物技术的突破为药物研发提供了新思路,一些小干扰RNA类药物,例如lumasiran和nedosiran,可分别选择性地降低肝脏乙醇酸氧化酶和乳酸脱氢酶表达,从而降低PH患者肝脏草酸生成和尿液草酸水平。CRISPR/Cas9等基因编辑技术也是PH潜在的治疗方法。本文将对PH基因治疗进展进行综述。

Primary hyperoxaluria(PH)is a rare autosomal recessive hereditary disease,characterized by calcium oxalate kidney stone and nephrocalcinosis caused by defects in enzymes of liver glyoxylate metabolism.Up to now,treatment options for PH are limited.Although medication treatment and liver transplantation can slow down the progression and mitigate the symptoms,the evidence for them turned out to be weak.In recent years,breakthroughs in biotechnology provide novel promising directions for drug development.Small interfering RNA drugs,such as lumasiran and nedosiran,selectively reduce hepatic expression of glycolate oxidase and lactate dehydrogenase respectively,reducing hepatic oxalate production and urinary oxalate levels in PH patients.Gene-editing,such as CRISPR/Cas9,will be a potential treatment method of PH.This review encompasses recent developments in the gene therapy of PH.