A Cure for Sanfilippo Syndrome? A Summary of Current Therapeutic Approaches and their Promise.
A Cure for Sanfilippo Syndrome? A Summary of Current Therapeutic Approaches and their Promise.
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DOI：
10.18103/mra.v8i2.2045
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发表时间：
2020-02-01
期刊：
影响因子：
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通讯作者：
Iacovino, Michelina
中科院分区：
文献类型：
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作者：
Pearse, Yewande;Iacovino, Michelina
粘多糖病III（MPS III，Sanfilippo综合征）是粘多糖病（MPS）的一种亚型，MPS是一组由负责分解代谢糖胺聚糖（GAG）的溶酶体酶缺乏引起的遗传性溶酶体疾病。虽然MPS III罕见，但MPS疾病作为一组相对常见，总发病率约为20，000 - 25，000例新生儿中的1例。MPS III是儿科疾病，会导致学习困难、行为障碍和痴呆，以及骨骼畸形，最终导致过早死亡。目前尚无获批的MPS III治疗方法，但许多治疗方法正在开发中。在过去的30年里，使用细胞和动物模型的研究已经导致了涉及酶替代疗法（ERT）、底物减少疗法（SRT）和基因疗法的临床试验，而干细胞方法仍然处于临床前阶段。虽然在动物模型中的安全性和临床疗效已显示出希望，但临床试验的结果已被证明是昂贵的，并显示出有限的治疗效果。在这篇综述中，我们描述了临床试验的最新结果。虽然ERT和基因治疗是MPS III最先进的治疗方法，但我们强调需要做的工作，以使我们更接近这些毁灭性疾病的真实的治疗。
Mucopolysaccharidoses III (MPS III, Sanfilippo syndrome) is a subtype of the Mucopolysaccharidoses (MPS), a group of inherited lysosomal disorders caused by a deficiency of lysosomal enzymes responsible for catabolizing glycosaminoglycans (GAGs). Although MPS III is rare, MPS diseases as a group are relatively frequent with an overall incidence of approximately 1 in 20,000 - 25,000 births. MPS III are paediatric diseases, which cause learning difficulties, behavioural disorders and dementia, as well as skeletal deformities and ultimately result in premature death. There are currently no approved treatments for MPS III, but a number of therapeutic approaches are under development. In the past 30 years, research using cellular and animal models have led to clinical trials involving enzyme replacement therapy (ERT), substrate reduction therapy (SRT) and gene therapy, while stem cells approaches remain at the pre-clinical stage. Although safety and clinical efficacy in animal models have shown promise, the results of clinical trials have proved costly and shown limited therapeutic effects. In this review, we describe the most recent results from clinical trials. While ERT and gene therapy are the most developed therapies for MPS III, we highlight the work that needs to be done to bring us closer to a real treatment for these devastating diseases.