Enzyme replacement therapy for mucopolysaccharidosis VI: long-term cardiac effects of galsulfase (Naglazyme®) therapy
Enzyme replacement therapy for mucopolysaccharidosis VI: long-term cardiac effects of galsulfase (Naglazyme®) therapy
复制标题
DOI：
10.1007/s10545-012-9481-2
复制
发表时间：
2013-03-01
影响因子：
4.2
通讯作者：
Harmatz, P.
中科院分区：
文献类型：
--
作者：
Braunlin, E.;Rosenfeld, H.;Harmatz, P.
特征性心脏瓣膜异常和左心室肥厚存在于未治疗的粘多糖病VI型（MPS VI）患者。在长期使用重组人芳基硫酸酯酶B （rhASB， rhn -乙酰半乳糖胺4-硫酸酯酶，galsulase, NaglazymeA）进行酶替代治疗（ERT）的受试者中进行心脏超声检查以调查这些发现。在rhASB的1/2期、2期和3期试验中，54名受试者在ERT开始前进行了研究，并以特定的间隔进行了长达96周的每周1 mg/kg的rhASB输注。在基线时，二尖瓣和主动脉瓣阻塞存在，并且在千分之一至12岁的人群中明显更大。存在轻度二尖瓣反流和微量主动脉反流，前者在< 12岁的患者中显著增加。左心室肥厚，平均z-评分比正常人高1.6-1.9 SD，年龄< 12岁和千分之一至12岁均存在。ERT治疗96周后，室间隔肥厚在< 12年的患者中消退。对于那些千分之一的人来说，间隔肥大没有改变，主动脉反流在统计上增加，但在生理上没有增加。二尖瓣和主动脉瓣的阻塞梯度保持不变。结果表明，对于12岁以下的儿童，长期ERT治疗可有效减少室间隔肥厚和防止心脏瓣膜异常进展。
Characteristic cardiac valve abnormalities and left ventricular hypertrophy are present in untreated patients with mucopolysaccharidosis type VI (MPS VI). Cardiac ultrasound was performed to investigate these findings in subjects during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB, rhN-acetylgalactosamine 4-sulfatase, galsulfase, NaglazymeA (R)). Studies were conducted in 54 subjects before ERT was begun and at specific intervals for up to 96 weeks of weekly infusions of rhASB at 1 mg/kg during phase 1/2, phase 2, and phase 3 trials of rhASB. At baseline, mitral and aortic valve obstruction was present and was significantly greater in those a parts per thousand yen12 years of age. Mild mitral and trace aortic regurgitation were present, the former being significantly greater in those < 12 years. Left ventricular hypertrophy, with averaged z-scores ranging from 1.6-1.9 SD greater than normal, was present for ages both < 12 and a parts per thousand yen12 years. After 96 weeks of ERT, ventricular septal hypertrophy regressed in those < 12 years. For those a parts per thousand yen12 years, septal hypertrophy was unchanged, and aortic regurgitation increased statistically but not physiologically. Obstructive gradients across mitral and aortic valves remained unchanged. The results suggest that long-term ERT is effective in reducing intraventricular septal hypertrophy and preventing progression of cardiac valve abnormalities when administered to those < 12 years of age.