AAV-mediated gene therapy for molybdenum cofactor deficiency type B

钼辅助因子缺乏症极为罕见，常染色体隐性遗传疾病，亚硫酸盐水平升高导致进行性神经退行性变。对于最常见的疾病（A型），可以使用生化替代疗法。其余大多数病例表现为B型钼辅助因子缺乏症，这是不可治疗的。在这方面，aav介导的基因治疗是最有希望的前景，这已经在动物模型中得到了非常有效的证明。迄今为止，由于缺乏合适的动物模型，这一成功原理的转移受到阻碍。该模型现在在申请人的组中可用。由于A型基因治疗的成功也在这个小组中得到了证实，因此将这种方法快速转移到迄今为止无法治愈的B型基因治疗似乎指日可待。这项研究旨在证明这一原理，并研究所有临床前可适应的参数。在项目结束时，临床研究应该是可行的。

The molybdenum cofactor deficiencies are extremely rare, autosomalrecessively inherited diseases, which by elevated sulfite levels lead to progressive neurodegeneration. For the most common form of the disease (type A) a biochemical substitutional therapy is available. Most of the remaining cases represent a type B molybdenum cofactor deficiency, which is not causally treatable. In this respect, AAV-mediated gene therapy is the most promising perspective, which was already demonstrated in an animal model for type very effectively. Transfer of this successful principle hitherto was hampered by the absence of a suitable animal model for this subform. This model is now available in the group of the applicant. Since the successful gene therapy of type A was also demonstrated by this group, the rapid transfer of this method to the hitherto incurable type B seems within reach. This study is meant to proof the principle and to study all preclinically amenable parameters. At the end of the project a clinical study should be feasible.