"Development of biglycan as a therapeutic for Duchenne Muscular Dystrophy"

“开发双聚糖治疗杜氏肌营养不良症”

• 批准号: 7738032
• 负责人: JUSTIN R. FALLON
• 金额: $ 133.24万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7738032
• 关键词: Development; biglycan; therapeutic; Duchenne; Muscular

DESCRIPTION (provided by applicant): This U01 Translational Research in Muscular Dystrophy will support the development 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. PUBLIC HEALTH RELEVANCE: In these translational studies we will develop a novel protein therapeutic for Duchenne Muscular Dystrophy. The goal is to take our findings in mouse models of this disease and do the work necessary to test this therapy in boys with this devastating disease. If the proposed work is successful, we will be able to move immediately into Phase I clinical trials.

描述（由申请人提供）：这项 U01 肌营养不良症转化研究将支持重组人双糖链蛋白聚糖 (rhBGN) 作为治疗药物的开发，并准备向 FDA 提交 IND 申请所需的数据包。它建立在我们实验室的探索性 R21 提案支持的工作基础上，我们已经证明，系统递送的 rhBGN 可以对抗 mdx 小鼠的营养不良表型并改善肌肉功能。值得注意的是，rhBGN 在每隔 3 周给药一次且剂量<10mg/kg 时有效。我们提出了一项为期 4 年的开发计划，以生产和验证与临床试验兼容的 rhBGN 材料。该计划将从使用瞬时转染产生的材料进行的试点研究延伸到 mdx 小鼠模型中的 PK/PD，再到使用在 cGMP 条件下稳定细胞系产生的高度特征化的材料进行剂量优化。为了最大限度地提高这一过程的效率和速度，这项工作将利用标准化模型和检测方法，以及与多家生物开发服务专家供应商的合作。我们还聘请了在生物制品特有的制造、测试和监管问题方面拥有丰富专业知识的顾问。 公共健康相关性：在这些转化研究中，我们将开发一种治疗杜氏肌营养不良症的新型蛋白质疗法。我们的目标是利用我们在这种疾病的小鼠模型中的发现，并做必要的工作，在患有这种毁灭性疾病的男孩身上测试这种疗法。如果拟议的工作成功，我们将能够立即进入第一阶段临床试验。