National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
J Inherit Metab Dis. 2024 Jan;47(1):63-79. doi: 10.1002/jimd.12665. Epub 2023 Aug 7.
Organic acidemias (OA) are a group of rare autosomal recessive disorders of intermediary metabolism that result in a systemic elevation of organic acid. Despite optimal dietary and cofactor therapy, OA patients still suffer from potentially lethal metabolic instability and experience long-term multisystemic complications. Severely affected patients can benefit from elective liver transplantation, which restores hepatic enzymatic activity, improves metabolic stability, and provides the theoretical basis for the pursuit of gene therapy as a new treatment for patients. Because of the poor outcomes reported in those with OA, especially methylmalonic and propionic acidemia, multiple gene therapy approaches have been explored in relevant animal models. Here, we review the results of gene therapy experiments performed using MMA and PA mouse models to illustrate experimental paradigms that could be applicable for all forms of OA.
有机酸血症（OA）是一组罕见的常染色体隐性遗传代谢紊乱，导致有机酸中毒全身性升高。尽管进行了最佳的饮食和辅助因子治疗，OA 患者仍患有潜在致命的代谢不稳定，并经历长期多系统并发症。严重受影响的患者可以从选择性肝移植中受益，肝移植可恢复肝酶活性，改善代谢稳定性，并为基因治疗作为患者的新治疗方法提供理论基础。由于 OA 患者，尤其是甲基丙二酸血症和丙酸血症患者的预后较差，因此已经在相关动物模型中探索了多种基因治疗方法。在这里，我们回顾了使用 MMA 和 PA 小鼠模型进行的基因治疗实验的结果，以说明可适用于所有 OA 形式的实验范例。
