Clément Lionel, Macé Camille
Glomerular disease therapeutics laboratory, Medicine/Division of Nephrology, university of Alabama at Birmingham, 1900 University boulevard, THT 611N, Birmingham, AL 35294, Étas-Unis.
Med Sci (Paris). 2016 Jun-Jul;32(6-7):606-11. doi: 10.1051/medsci/20163206024. Epub 2016 Jul 12.
Current therapies used in minimal change disease (MCD) were originally designed to cure other diseases. They are only partially efficient, and present inconvenient side effects. Therefore, understanding the molecular mechanisms implicated in the pathogenesis of proteinuria in MCD could lead to new therapeutic strategies. A new experimental transgenic rat model of human MCD was generated. These NPHS2-Angptl4 transgenic rats over-express two different forms of the glycoprotein Angptl4 from the podocyte. The majority of the protein shows a lack of sialylation that is implicated in the pathogenesis of proteinuria. Supplementation of ManNAc, a precursor of sialic acid, significantly reduces albuminuria in those rats by increasing sialylation of the hyposialylated form of Angptl4. After treatment of the first episode of MCD with glucocorticoids in patients, ManNAc could be used as a maintenance drug, especially to reduce the frequency and intensity of relapse. ManNAc is a promising therapeutic agent for patients with MCD.
微小病变病（MCD）目前使用的治疗方法最初是为治疗其他疾病而设计的。它们仅部分有效，且存在不便的副作用。因此，了解MCD中蛋白尿发病机制所涉及的分子机制可能会带来新的治疗策略。一种新的人类MCD实验性转基因大鼠模型被构建出来。这些NPHS2-Angptl4转基因大鼠从足细胞中过度表达两种不同形式的糖蛋白血管生成素样蛋白4（Angptl4）。大多数蛋白质显示出缺乏唾液酸化，这与蛋白尿的发病机制有关。补充唾液酸的前体N-乙酰甘露糖胺（ManNAc）可通过增加低唾液酸化形式的Angptl4的唾液酸化，显著降低这些大鼠的蛋白尿。在患者首次发作MCD用糖皮质激素治疗后，ManNAc可作为维持药物使用，特别是用于减少复发的频率和强度。ManNAc是一种有前景的MCD患者治疗药物。
