一项在犬类身上做的新的研究报告说，在出生的时候进行酶替代疗法可制止几乎所有的与一种罕见的遗传性疾病有关的问题。 这些发现凸显了对新生儿进行粘多糖贮积症I型这种疾病（或称MPS I）进行筛检的必要性，因为这是改善患者生活的最有效的方法。 该研究第一次显示，用酶替代疗法治疗MPS I可显著减少心脏、骨骼和脑部的疾病症状；它可能会给罹患类似遗传性疾病患者的输送酶的方法的改善。 粘多糖贮积症是一组溶酶体贮积病。 患有溶酶体贮积病的人常常缺失一种关键酶，这些酶所帮助分解的物质是身体所需的构建骨骼、软骨、肌腱、角膜、皮肤及结缔组织的物质。 MPS I是因为在编码α-L-艾杜糖醛酸苷酶这种溶酶体酶的基因中的一种缺陷所引起的；因此，受到影响的细胞或是无法产生这种酶或是其产生的酶量很低。
目前，人们还无法治愈这种疾病，但酶替代疗法是人们的一种通过注射形式将酶还给患者的尝试，这种疗法与基因疗法相似。但是，它又与基因疗法不同。酶替代疗法所提供病人的是一种缺失的基因产物（即酶），而不是提供身体制造该缺失产物的基因。现在，Andrew Ellinwood、Ashley Dierenfeld及其同事给罹患MPS I的新出生的犬注射高剂量的α-L-艾杜糖醛酸苷酶。他们发现，在早期开始酶替代疗法可令人惊异地防止MPS I疾病的几乎所有的方面（甚至包括在脑中的病变）。以往的酶替代疗法研究（在年龄较长患者中所进行的）只能够轻度地减少MPS I的症状。早期治疗防止了溶酶体物质在肝脏、脾脏、肾脏和心脏中的累积；这提示，酶替代疗法具有在症状出现之前在宝宝中消灭MPS I的潜力。此外，现在已经有一种在出生之时发现罹患MPS I孩子的测试方法。>
推荐原文出处：
Sci Transl Med DOI: 10.1126/scitranslmed.3001380
Replacing the Enzyme α-l-Iduronidase at Birth Ameliorates Symptoms in the Brain and Periphery of Dogs with Mucopolysaccharidosis Type I
Ashley D. Dierenfeld1, Michael F. McEntee2, Carole A. Vogler3, Charles H. Vite4, Agnes H. Chen5, Merry Passage5, Steven Le5, Sahil Shah5, Jackie K. Jens1, Elizabeth M. Snella1, Karen L. Kline6, Jennifer D. Parkes6, Wendy A. Ware6, Lori E. Moran6, Amanda J. Fales-Williams7, Jane A. Wengert6, R. David Whitley6, Daniel M. Betts6, Amy M. Boal6, Elizabeth A. Riedesel6, William Gross6, N. Matthew Ellinwood1,6,* and Patricia I. Dickson5
Abstract
Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by loss of activity of α-l-iduronidase and attendant accumulation of the glycosaminoglycans dermatan sulfate and heparan sulfate. Current treatments are suboptimal and do not address residual disease including corneal clouding, skeletal deformities, valvular heart disease, and cognitive impairment. We treated neonatal dogs with MPS I with intravenous recombinant α-l-iduronidase replacement therapy at the conventional 0.58 mg/kg or a higher 1.57 mg/kg weekly dose for 56 to 81 weeks. In contrast to previous results in animals and patients treated at a later age, the dogs failed to mount an antibody response to enzyme therapy, consistent with the induction of immune tolerance in neonates. The higher dose of enzyme led to complete normalization of lysosomal storage in the liver, spleen, lung, kidney, synovium, and myocardium, as well as in the hard-to-treat mitral valve. Cardiac biochemistry and function were restored, and there were improvements in skeletal disease as shown by clinical and radiographic assessments. Glycosaminoglycan levels in the brain were normalized after intravenous enzyme therapy, in the presence or absence of intrathecal administration of recombinant α-l-iduronidase. Histopathological evidence of glycosaminoglycan storage in the brain was ameliorated with the higher-dose intravenous therapy and was further improved by combining intravenous and intrathecal therapy. These findings argue that neonatal testing and early treatment of patients with MPS I may more effectively treat this disease.
Footnotes
Citation: A. D. Dierenfeld, M. F. McEntee, C. A. Vogler, C. H. Vite, A. H. Chen, M. Passage, S. Le, S. Shah, J. K. Jens, E. M. Snella, K. L. Kline, J. D. Parkes, W. A. Ware, L. E. Moran, A. J. Fales-Williams, J. A. Wengert, R. D. Whitley, D. M. Betts, A. M. Boal, E. A. Riedesel, W. Gross, N. M. Ellinwood, P. I. Dickson, Replacing the Enzyme α-L-Iduronidase at Birth Ameliorates Symptoms in the Brain and Periphery of Dogs with Mucopolysaccharidosis Type I. Sci. Transl. Med. 2, 60ra89 (2010).
