SYR Lee, STS Lam, DKK Ng, KY Chan, KW Ng

Abstract

In this article, we review specific therapies that tackle the basic biochemical defects of lysosomal storage diseases. These include bone marrow transplantation, substrate deprivation therapy, enzyme replacement therapy and enzyme enhancement therapy. We particularly update the progress of development of enzyme replacement therapy, which plays a major role in the treatment of lysosomal storage diseases. Nowadays, enzyme products have been developed and marketed for treatment of Gaucher disease, Fabry disease, mucopolysaccharidosis I and currently there are ongoing trials of enzyme replacement for the treatment of glycogen storage disease II, mucopolysaccharidosis II and VI and Niemann-Pick B disease. Enzyme replacement therapy has a definite role in treatment of lysosomal storage diseases as it can ameliorate the signs and symptoms of the diseases. However, there are certain limitations. Enzyme replacement therapy is ineffective in improving or preventing neurological involvement. Response to treatment is slow in some situations, for example, bone involvement in Gaucher disease. It may also be unpredictable in other situations, for example, lung involvement in Gaucher disease. Hence, there is room for incorporation of other treatment modalities. One example is provided by mucopolysaccharidosis type I, in which bone marrow transplantation has a definite role as it prevents psychomotor retardation when carried out before significant brain damage occurs.

在這篇文章中，我們對具有基礎生化缺陷的溶酶體貯積病的特異療法進行了綜述。這些療法包括骨髓移植療法、底物剝奪療法，酶替代療法及酶增強療法。我們特別更新了酶替代療法發展的進展，它在溶酶體貯積病的治療中扮演了主要的角色。現今，用於治療 Gaucher 病、Fabry 病、粘多糖病 I 型的酶的產品已經發展並市場化；而為治療 II 型糖原累積症、II 及 VI 型粘多糖病及 B 型尼曼-匹克病的酶替代療法試驗正在進行。酶替代療法在治療溶酶體貯積病中扮演了確定的角色，因為它能夠改善這些疾病的症侯。然而，這個療法有一定的限制。酶替代療法在改善或阻止神經系統的累及上效率不高。在一些情況下，如 Gaucher 病的病人骨骼受影響，療效便不太顯注。在其他情況下，如 Gaucher 病的病人肺部受影響，療效也許是不可預測的。因此，存在與其他的療法結合治療溶酶體貯積病的空間。粘多糖病 I 型是一個例子，骨髓移植在該病的治療上扮演了確定的角色，因為它阻止了嚴重的腦損害發生之前，精神性運動遲滯的進展。