Department of Medical and Surgical Sciences, Pediatrics Unit, University "Magna Graecia", Catanzaro, Italy.
Curr Gene Ther. 2018;18(2):90-95. doi: 10.2174/1566523218666180404155759.
Mucopolysaccharidosis type II or Hunter syndrome is an X-linked lysosomal storage disease caused by a mutation in the gene encoding the lysosomal enzyme iduronate-2-sulfatase. The consequent enzyme deficiency causes a progressive, multisystem accumulation of glycosaminoglycans, which is the cause of the clinical manifestations involving also Central Nervous System for patients with the severe form of disease. The limits of the currently available therapies for Hunter syndrome, hematopoietic stem cell transplantation and recombinant enzyme replacement therapy, mainly regarding brain achievement, have encouraged several studies which recognized gene therapy as a potential therapeutic option for this condition. In vitro studies firstly aimed at the demonstration that viral vector- mediated IDS gene expression could lead to high levels of enzyme activity in transduced cells. The encouraging results obtained allowed the realization of many preclinical studies investigating the utilization of gene therapy vectors in animal models of Mucopolysaccharidosis II, together with a phase I clinical trial approved for Hunter patients affected by the mild form of the disease. Together to in vivo studies in which recombinant vectors are directly administered, systematically or by direct injection into Central Nervous System, also ex vivo gene therapy, consisting in transplantation of autologous hematopoietic stem cells, modified in vitro, into the animal or patient, has been tested. A wider clinical application of the results obtained so far is essential to ensure that gene therapy can be definitively validated as a therapeutic option available and usable for this rare but life-threatening disorder.
黏多糖贮积症 II 型（Hunter 综合征）是一种 X 连锁溶酶体贮积病，由编码溶酶体酶艾杜糖-2-硫酸酯酶的基因突变引起。由此导致的酶缺乏导致糖胺聚糖在体内进行性、多系统积累，这也是导致包括中枢神经系统在内的临床表现的原因，对于疾病的严重形式的患者而言。目前 Hunter 综合征的治疗方法（造血干细胞移植和重组酶替代疗法）存在局限性，主要是针对大脑方面的疗效，这促使了多项研究将基因治疗视为这种疾病的潜在治疗选择。体外研究首先旨在证明病毒载体介导的 IDS 基因表达可以导致转导细胞中酶活性的高水平。令人鼓舞的研究结果使得可以进行许多临床前研究，调查基因治疗载体在黏多糖贮积症 II 型动物模型中的利用，以及一项针对受疾病轻度影响的 Hunter 患者的 I 期临床试验。除了体内研究（其中重组载体被直接给予，系统地或通过直接注射到中枢神经系统）之外，还测试了离体基因治疗，即通过体外修饰的自体造血干细胞移植到动物或患者中。为了确保基因治疗可以被明确验证为一种可用的治疗选择，并可用于这种罕见但危及生命的疾病，扩大迄今获得的研究结果的临床应用至关重要。
