BIOMEDICAL (APPLIED/EXPLORATORY)

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）是目前铁螯合治疗的“金标准”，已使用了40多年。 问题包括患者不依从，快速过滤到尿液中的现象，将给药剂量确定为克级。 该提案的目的是通过允许DFO包封在具有延长的循环时间的组织靶向脂质体中（即聚乙二醇化）来开发新的、更有效的DFO制剂。 这将导致使用显著更低的DFO剂量进行更有效的铁螯合。 新型聚乙二醇化制剂（peg-LDFO）将进行完整的生物分布研究，以及与游离DFO的动物试验比较。 在第1阶段开发的最佳配方将产生一种新药，最终将显着减少患者的铁过载，消除对泵输送的需要，降低治疗成本，并提高患者的依从性。 第二阶段将最后确定配方，为临床研究做准备。 这种疗法适用于一类孤儿疾病，这些疾病通常折磨贫困和被剥夺权利的人群;因此，商业机会是全球性的。

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.