The absence of adenosine deaminase (ADA) causes severe combined immune deficiency (SCID), which has been treated with PEGylated bovine-extracted ADA (ADAGEN). ADAGEN was recently replaced by a PEGylated recombinant bovine ADA, expressed in Escherichia coli (elapegademase, ELA-ADA). Limited information on ELA-ADA is available. ADA enzymatic activity of ELA-ADA and ADAGEN was assessed in vitro at diverse dilutions. ADA activity and immune reconstitution in an ADA-SCID patient treated with ELA-ADA were compared with age-matched patients previously treated with ADAGEN. ADA activity and thymus reconstitution were evaluated in ADA-deficient mice following ELA-ADA or ADAGEN administered from 7 days postpartum. In vitro, ADA activity of ELA-ADA and ADAGEN were similar at all dilutions. In an ADA-SCID patient, ELA-ADA treatment led to a marked increase in trough plasma ADA activity, which was 20% higher than in a patient previously treated with ADAGEN. A marked increase in T cell numbers and generation of naive T cells was evident following 3 months of ELA-ADA treatment, while T cell numbers increased following 4 months in 3 patients previously treated with ADAGEN. T cell proliferations stimulation normalized and thymus shadow became evident following ELA-ADA treatment. ADA activity was significantly increased in the blood of ADA-deficient mice following ELA-ADA compared to ADAGEN, while both treatments improved the mice weights, the weight, number of cells in their thymus and thymocyte subpopulations. ELA-ADA has similar in- vitro and possibly better in-vivo activity than ADAGEN. Future studies will determine whether ELA-ADA results in improved long-term immune reconstitution.

中文翻译：

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ADA缺陷患者和小鼠中elapegademase和pegademase的比较。

腺苷脱氨酶（ADA）的缺乏会导致严重的联合免疫缺陷症（SCID），已经用聚乙二醇化牛提取的ADA（ADAGEN）对其进行了治疗。ADAGEN最近被在大肠杆菌中表达的聚乙二醇化重组牛ADA取代（elapegademase，ELA-ADA）。提供有关ELA-ADA的有限信息。在体外以不同的稀释度评估了ELA-ADA和ADAGEN的ADA酶活性。将接受ELA-ADA治疗的ADA-SCID患者的ADA活性和免疫重建与先前接受ADAGEN治疗的年龄相匹配的患者进行比较。从产后7天开始服用ELA-ADA或ADAGEN后，在ADA缺陷小鼠中评估ADA活性和胸腺重构。在体外，ELA-ADA和ADAGEN的ADA活性在所有稀释度下均相似。在ADA-SCID患者中，ELA-ADA治疗导致槽血浆ADA活性显着增加，比先前用ADAGEN治疗的患者高20％。在接受ELA-ADA治疗3个月后，T细胞数量和幼稚T细胞的生成量明显增加，而在3个月之前接受ADAGEN治疗的患者中，T细胞数量增加。在ELA-ADA治疗后，T细胞增殖刺激恢复正常，并且胸腺阴影变得明显。与ADAGEN相比，ELA-ADA后ADA缺陷小鼠的血液中ADA活性显着增加，而两种治疗均改善了小鼠的体重，体重，胸腺细胞数量和胸腺细胞亚群。ELA-ADA在体外具有相似的活性，并且体内活性可能比ADAGEN高。