The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher's disease
The efficacy of enzyme replacement therapy in patients with chronic neuronopathic Gaucher's disease
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DOI：
10.1067/mpd.2001.112171
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发表时间：
2001-04-01
影响因子：
5.1
通讯作者：
Tournay, A
中科院分区：
文献类型：
--
作者：
Altarescu, G;Hill, S;Tournay, A
目的：评价应用巨噬细胞靶向葡萄糖脑苷酶的酶替代疗法(ERT)对3型高谢病患者的长期全身和神经学反应。研究设计：对21例8个月至35岁的3型高谢病患者进行前瞻性研究。调整酶剂量以控制全身症状。临床和实验室评估在基线时和之后每6至12个月进行一次。结果：患者的血红蛋白水平、血小板计数和酸性磷酸酶值均有明显改善。肝脾体积明显缩小，骨结构改善。19例对ERT反应不佳的无症状间质性肺疾病。核上性凝视麻痹19例保持稳定，1例恶化，1例改善。13例患者的认知功能随着时间的推移保持不变或改善，但8例患者的认知功能下降，其中3例发展为进行性肌阵挛脑病，并伴有头颅磁共振成像和脑电恶化。结论：在相对较高的剂量下，ERT几乎逆转了3型Gaucher病患者的所有全身表现。大多数接受治疗的患者在神经学上不会恶化，需要新的治疗策略来逆转疾病的肺部和神经病变方面。
Objective: To assess the long-term systemic and neurologic responses to enzyme replacement therapy (ERT) with macrophage-targeted glucocerebrosidase in patients with type 3 Gaucher's disease.Study design: Patients with type 3 Gaucher's disease (n = 21), aged 8 months to 35 years, were enrolled in a prospective study. Enzyme dose was adjusted to control systemic manifestations. Clinical and laboratory evaluations were performed at baseline and every 6 to 12 months thereafter. Patients were followed up for 2 to 8 years.Results: Significant improvement in hemoglobin levels, platelet count, and acid phosphatase values occurred. Liver and spleen volume markedly decreased, and bone structure improved. Nineteen patients bad asymptomatic interstitial lung disease unresponsive to ERT. Supranuclear gaze palsy remained stable in 19 patients, worsened in one patient, and improved in one. Cognitive function remained unchanged or improved over time in 13 patients but decreased in 8 patients, 3 of whom developed progressive myoclonic encephalopathy accompanied by cranial magnetic resonance imaging and electroencephalographic deterioration.Conclusions: At relatively high doses, ERT reverses almost all the systemic manifestations in patients with type 3 Gaucher's disease. Most treated patients do not deteriorate neurologically, Novel therapeutic strategies are required to reverse the pulmonary and neuronopathic aspects of the disease.