Development of biglycan as a therapeutic for Duchenne Muscular Dystrophy

这项针对血管性营养不良的U01翻译研究将支持重组人的发展 Biglycan(重组人BGN)作为一种治疗药物，并准备向FDA提交IND文件所需的数据包。 它建立在由我们实验室的探索性R21提案支持的工作基础上，我们的实验室拥有 证明了系统递送的，重组人BGN对抗mdx小鼠和 改善肌肉功能。值得注意的是，重组人BGN每隔3周给药一次，剂量为 &lt；10 mg/kg。我们提出了一个4年的发展计划，以生产和验证重组人BGN材料，即 与临床试验中的使用兼容。该计划将从试验性研究延伸到由 瞬时转染法，在mdx小鼠模型中对PK/PD进行剂量优化，具有高度的特征性 在cGMP条件下由稳定的细胞系产生的物质。要最大限度地提高效率和速度 在这一过程中，这项工作将利用标准化的模型和分析以及与 几家专业的生物开发服务供应商。我们还聘请了顾问，他们已经 在生物独特的制造、测试和监管问题上拥有丰富的专业知识。

This U01 Translational Research in iVluscular Dystrophy will support the deveiopment of recombinant human biglycan (rhBGN) as a therapeutic and to prepare the data package necessary for an IND filing with the FDA. It builds upon work supported by an exploratory R21 proposal to our laboratory where we have demonstrated that systemically-delivered, rhBGN counters the dystrophic phenotype in mdx mice and improves muscle function. Notably, rhBGN is effective when delivered at 3 week intervals and at doses of <10mg/kg. We propose a 4 year development plan to produce and to validate rhBGN material that is compatible with use in clinical trials. This plan will extend from pilot studies with material produced by transient transfection, to PK/PD in the mdx mouse model, to dose optimization with highly characterized material produced from a stable cell line under cGMP conditions. To maximize the efficiency and speed of this process, the work will make use of standardized models and assays as well as collaborations with several expert vendors of biologic development services. We have also enlisted consultants who have extensive expertise in the manufacturing, testing and regulatory issues that are unique to biologies.