Glucose tetrasaccharide as a biomarker for monitoring the therapeutic response to enzyme replacement therapy for Pompe disease
Glucose tetrasaccharide as a biomarker for monitoring the therapeutic response to enzyme replacement therapy for Pompe disease
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DOI：
10.1016/j.ymgme.2005.03.010
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发表时间：
2005-08-01
影响因子：
3.8
通讯作者：
Chen, YT
中科院分区：
文献类型：
--
作者：
An, Y;Young, SP;Chen, YT
四葡萄糖低聚物Glc α 1- 6 Glc α 1- 4Glc α 1-4Glc，命名为Glc（4），已被证明是诊断庞贝氏症的推定生物标志物。本研究的目的是评估Glc（4）是否可用于监测庞贝氏症患者对重组人酸性α葡萄糖苷酶（rhGAA）酶替代疗法（ERT）的治疗反应。通过HPLC-UV和稳定同位素稀释ESI-MS/MS测定接受rhGAA治疗的II型患者的尿Glc（4）水平。仅通过HPLC-UV测定这些患者血浆中Glc（4）和麦芽四糖Glc α 1 - 4Glc α 1 - 4Glc α 1 -4Glc（M-4）的组合浓度，命名为Hex（4）。这些患者的基线尿Glc 4和血浆Hex（4）（平均值+/- SD：分别为34.2 +/- 11.3 mmol/mol肌酐和1.7 +/- 0.8 μ M）高于年龄匹配的对照值（平均值+/- SE），分别为6.1 +/- 5.1 mmol/mol肌酐和0.22 +/- 0.15 μ M）。所有患者开始ERT后，尿Glc 4和血浆Hex（4）水平均降低。在骨骼肌和心肌中具有最佳总体临床应答的4名患者中，在治疗的第一年期间水平降低至正常水平内或接近正常水平。相比之下，在临床应答较差（心脏应答良好但运动改善有限）的患者中，水平波动并持续升高至对照范围以上。这些结果表明，尿Glc（4）和血浆Hex（4）可作为临床终点的有价值辅助指标，用于监测治疗干预措施（如rhGAA ERT）在庞贝氏症中的疗效。(c)2005年爱思唯尔公司All rights reserved.
A tetraglucose oligomer, Glc alpha 1-6Glc alpha 1-4Glc alpha 1-4Glc, designated Glc(4), has been shown to be a putative biomarker for the diagnosis of Pompe disease. The purpose of this study was to assess whether Glc(4) could be used to monitor the therapeutic response to recombinant human acid alpha glucosidase (rhGAA) enzyme replacement therapy (ERT) in patients with Pompe disease. Urinary Glc(4) levels in I I patients receiving rhGAA therapy was determined by both HPLC-UV and stable isotope dilution ESI-MS/MS. Combined Glc(4) and maltotetraose, Glc alpha 1-4Glc alpha 1-4Glc alpha 1-4Glc, (M-4) concentrations, designated Hex(4), in plasma from these patients were measured by HPLC-UV only. Baseline urinary Glc4 and plasma Hex(4) in these patients (mean +/- SD: 34.2 +/- 11.3 mmol/mol creatinine and 1.7 +/- 0.8 mu M, respectively) were higher than age-matched control values (mean +/- SE), 6.1 +/- 5.1 mmol/mol creatinine and 0.22 +/- 0.15 mu M, respectively). Both urinary Glc4 and plasma Hex(4) levels decreased after initiation of ERT for all patients. In the four patients with the best overall clinical response in both skeletal and cardiac muscle, levels decreased to within, or near, normal levels during the first year of treatment. In contrast, levels fluctuated and were persistently elevated above the control ranges in those patients with a less favorable clinical response (good cardiac response but limited motor improvement). These results suggest that urinary Glc(4) and plasma Hex(4) could serve as a valuable adjunct to clinical endpoints for monitoring the efficacy of therapeutic interventions such as rhGAA ERT in Pompe disease. (c) 2005 Elsevier Inc. All rights reserved.