PRODUCTION OF BETA-GLUCURONIDASE FOR MPS VII

说明(申请人摘要)：酶的缺陷 β-葡萄糖醛酸苷导致进行性衰弱和致命性疾病 粘多糖代谢紊乱被称为MPS VII或SLY疾病。 第一批MPS被酶学鉴定，并已在 人类和动物模型。关于该病治疗的大量数据 存在于小鼠模型中，没有将基准研究翻译到人类患者 曾经发生过，部分原因是MPS VII的明显稀有。 这项研究的长期目标是开发一种酶 MPSVII患者的替代疗法。这项工作将由以下人员完成 在第一阶段开发高产细胞系，然后开发 在第二阶段完成一个完整的商业流程。该战略将利用 为MPS I酶替代开发的现有设施和程序 计划迅速转移到符合GMP要求的酶的生产。这项工作 从而为提交IND和酶的临床试验奠定基础 MPS VII患者的替代治疗。 建议的商业应用： 从这项工作中产生的酶和方法可用于生产酶和 治疗患有粘多糖病VII的患者，这是一种严重的、危及生命的基因 无序。

DESCRIPTION (applicant's abstract): The deficiency of the enzyme beta-glucuronidaseleads to a progressive debilitatingand fatal disorder of mucopolysaccharidemetabolism known as MPS VII orSly disease.This disorderwas the first MPS to beidentified enzymatically and has been studiedextensively in humansand animalmodels. Thoughextensive data on thetreatment of thedisease exists in the mousemodel, no translation of the benchresearch to human patients has ever occurred due inpart to the apparent rarity of MPS VII. The keylong-term objective of this research is thedevelopment of an enzyme replacementtherapy for MPSVII patients. Thework will be accomplished by developing a highly productive cell line in phase I followed by thedevelopment of a complete commercial process in phase II. The strategy will exploit existing facilities and procedures developed for MPS I enzyme replacement program to rapidly move to theproduction of enzyme in GMP compliance. The work would thus set thestage for filing of an IND and a clinical trial of enzyme replacement therapy in MPS VII patients. PROPOSED COMMERCIAL APPLICATION: The enzyme and process created from this work can be used to produce enzyme and treat patients suffering from Mucopolysaccharidosis VII, a serious, life-threatening genetic disorder.