BIOMEDICAL (APPLIED/EXPLORATORY)

生物医学（应用/探索）

• 批准号: 7934246
• 负责人: Judith K Gwathmey
• 金额: $ 27.91万
• 依托单位: GWATHMEY, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7934246
• 关键词: BIOMEDICAL; APPLIED; EXPLORATORY

Transfusion-related iron overload is a major cause of morbidity and mortality in patients with a variety of transfusion- dependant anemias, including sickle cell anemia and thalassemia major. Desferrioxamine (DFO), the current "gold standard" in iron chelation therapy, has been used for over 40 years. Problems include patient non-compliance the phenomenon of rapid filtration into the urine establishing the administered dosage to gram levels. The aim of this proposal is the development of new, more effective formulations of DFO by allowing entrapment of DFO in tissue-targeted liposomes with prolonged circulation times (i.e. pegylated). This will result in a more effective iron chelation using significantly lower DFO dosage. The novel pegylated formulation (peg-LDFO) will undergo complete biodistribution studies, as well as animal test comparisons with free DFO. The optimal formulation developed during Phase 1 will result in a new drug that eventually will significantly reduce patient iron overload, eliminate the need for pump delivery, reduce treatment cost, and increase patient compliance. Phase II will finalize the formulation in preparation for clinical studies. This therapy applies to a category of orphan diseases which typically afflict impoverished and disenfranchised populations; therefore, commercial opportunity is global.

输血相关的铁超负荷是各种输血依赖性贫血（包括镰状细胞性贫血和重型地中海贫血）患者发病和死亡的主要原因。 去铁胺 (DFO) 是目前铁螯合疗法的“金标准”，已使用 40 多年。 问题包括患者不遵守快速过滤到尿液中的现象，从而确定给药剂量达到克水平。 该提案的目的是通过将 DFO 包埋在组织靶向脂质体中并延长循环时间（即聚乙二醇化），开发新的、更有效的 DFO 制剂。 这将使用显着较低的 DFO 剂量实现更有效的铁螯合。 新型聚乙二醇化制剂 (peg-LDFO) 将接受完整的生物分布研究，以及与游离 DFO 的动物试验比较。 第一阶段开发的最佳配方将产生一种新药，最终将显着降低患者铁过载，消除泵输送的需要，降低治疗成本并提高患者依从性。 第二阶段将最终确定配方，为临床研究做准备。 这种疗法适用于一类罕见疾病，这些疾病通常困扰贫困和被剥夺公民权的人群；因此，商业机会是全球性的。