Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824, USA.
Curr Pharm Des. 2011;17(24):2558-74. doi: 10.2174/138161211797247578.
Lysosomal Storage Diseases (LSDs) comprise a group of over fifty inherited metabolic disorders, with their hallmark feature being deficient catabolism and accumulation (storage) of macromolecules in the lysosomes due to genetic deficiency of specific lysosomal enzymes. The combined incidence of LSDs is estimated to be ~1 in 7,000 births. LSD symptoms can vary significantly, primarily due to the nature of the gene defect (null or missense mutations) as well as which cells are affected. Cumulatively, LSDs place a significant burden on patients and their families, causing much in the way of morbidity and mortality. Currently, there is no cure for any LSD. This review will describe currently available treatment options for LSD patients, and then focus upon gene therapy prospects for various LSDs. Worldwide, researchers have accumulated significant data in humans affected by LSDs, as well as several small and large animal models. As a result, various viral and non-viral gene transfer platforms have been developed and specifically optimized to treat LSDs. In this review we will describe advances suggesting that the LSDs may be some of the most amenable diseases to treat by gene therapy based approaches. However, to overcome the several remaining limitations encountered by these approaches, a deep understanding of the biology of the LSDs is required, as well as the host innate and adaptive immune responses to the act of gene transfer.
溶酶体贮积症（LSDs）是一组超过五十种遗传性代谢紊乱疾病，其特征是由于特定溶酶体酶的遗传缺陷，导致大分子在溶酶体中代谢不足和积累（储存）。LSD 的综合发病率估计为每 7000 例出生中有 1 例。LSD 的症状差异很大，主要是由于基因缺陷的性质（缺失或错义突变）以及受影响的细胞类型。累积起来，LSD 给患者及其家属带来了巨大的负担，导致了大量的发病率和死亡率。目前，任何 LSD 都没有治愈方法。本综述将描述目前 LSD 患者的治疗选择，然后重点介绍各种 LSD 的基因治疗前景。在全球范围内，研究人员在受 LSD 影响的人类以及几种小型和大型动物模型中积累了大量数据。因此，已经开发并专门优化了各种病毒和非病毒基因转移平台来治疗 LSD。在本综述中，我们将描述一些进展，表明 LSD 可能是最适合通过基因治疗方法治疗的疾病之一。然而，为了克服这些方法遇到的几个剩余限制，需要深入了解 LSD 的生物学特性，以及宿主对基因转移的固有和适应性免疫反应。
