一項在犬類身上做的新的研究報告說，在出生的時候進行酶替代療法可制止幾乎所有的與一種罕見的遺傳性疾病有關的問題。 這些發現凸顯了對新生兒進行粘多糖貯積症I型這種疾病（或稱MPS I）進行篩檢的必要性，因為這是改善患者生活的最有效的方法。 該研究第一次顯示，用酶替代療法治療MPS I可顯著減少心臟、骨骼和腦部的疾病症狀；它可能會給罹患類似遺傳性疾病患者的輸送酶的方法的改善。 粘多糖貯積症是一組溶酶體貯積病。 患有溶酶體貯積病的人常常缺失一種關鍵酶，這些酶所幫助分解的物質是身體所需的構建骨骼、軟骨、肌腱、角膜、皮膚及結締組織的物質。 MPS I是因為在編碼α-L-艾杜糖醛酸苷酶這種溶酶體酶的基因中的一種缺陷所引起的；因此，受到影響的細胞或是無法產生這種酶或是其產生的酶量很低。
目前，人們還無法治癒這種疾病，但酶替代療法是人們的一種通過注射形式將酶還給患者的嘗試，這種療法與基因療法相似。但是，它又與基因療法不同。酶替代療法所提供病人的是一種缺失的基因產物（即酶），而不是提供身體製造該缺失產物的基因。現在，Andrew Ellinwood、Ashley Dierenfeld及其同事給罹患MPS I的新出生的犬注射高劑量的α-L-艾杜糖醛酸苷酶。他們發現，在早期開始酶替代療法可令人驚異地防止MPS I疾病的幾乎所有的方面（甚至包括在腦中的病變）。以往的酶替代療法研究（在年齡較長患者中所進行的）只能夠輕度地減少MPS I的症狀。早期治療防止了溶酶體物質在肝臟、脾臟、腎臟和心臟中的累積；這提示，酶替代療法具有在症狀出現之前在寶寶中消滅MPS I的潛力。此外，現在已經有一種在出生之時發現罹患MPS I孩子的測試方法。 （生物谷Bioon.com）
生物谷推薦原文出處：
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).