THERAPEUTIC APPLICATIONS OF MICROBUBBLES-PHASE II

微泡第二阶段的治疗应用

基本信息

批准号：
6207624
负责人：
THOMAS R PORTER
金额：
$ 42.43万
依托单位：
AVI BIOPHARMA, INC.
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-09-30 至 2002-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6207624
关键词：
albumins antisense nucleic acid clinical research coronary occlusion /thrombosis fibrinolysis fluosol gene therapy glucose human subject hyperplasia laboratory rat microcapsule nonhuman therapy evaluation oligonucleotides protooncogene restenosis swine ultrasound therapy

项目摘要

The long term objective of this project is to utilize the multiple therapeutic properties of perfluorocarbon containing albumin coated microbubbles to non-invasively target synthetic gene therapy and recanalize thrombosed access grafts and coronary arteries. The ability of intravenous perfluorocarbon containing albumin microbubbles to bind and deliver antisense oligonucleotides to the c-myc protoncogene into the endothelium following intracoronary stent deployment will be quantified, and then tested in humans to determine whether it significantly reduces restenosis. Secondly, the ability of these intravenous microbubbles to microfragment arterial thrombi in the presence of low frequency ultrasound will be prospectively evaluated to determine whether it can replace current pharmacologic and surgical techniques in recanalizing thrombosed renal dialysis grafts. The ability of perfluorocarbon containing microbubbles to both recanalize acute coronary thromboses and diffuse oxygen from the lungs to ischemic tissue will be combined to determine how these properties can improve the clinical outcome of patients with acute coronary syndromes. Finally, the ability of perfluorocarbon containing microbubbles to induce atrial and ventricular paced rhythms in the presence of low frequency ultrasound will be assessed in patients undergoing electrophysiologic testing. These multi-faceted investigations will provide the framework for the use of microbubbles as an alternative or supplement to current cardiovascular therapies. PROPOSED COMMERCIAL APPLICATION: In addition to diagnostic applications, perfluorocarbon containing albumin microbubbles may have several therapeutic applications. First, they could be a noninvasive method of targeting the delivery of specific intravenous antisense oligonucleotides to damaged endothelium. They can also target the delivery of oxygen to ischemic tissue. In the presence of transcutaneous low frequency ultrasound, they cavitate and break up intra arterial thrombi. Therefore, they may be an alternative or supplement to fibrinolytic therapy in treating hemodialysis access graft thrombosis or acute coronary syndromes.

该项目的长期目标是利用含有白蛋白涂层微泡的全氟化碳的多种治疗特性，以非侵入性靶向合成基因治疗并重新疏通血栓接入移植物和冠状动脉。在冠状动脉内支架展开后，静脉内含有全氟化碳的白蛋白微泡与c-myc原癌基因结合并将反义寡核苷酸递送至内皮的能力将被量化，然后在人体中进行测试以确定其是否显着减少再狭窄。其次，将前瞻性地评估这些静脉内微泡在低频超声存在下微碎动脉血栓的能力，以确定其是否可以取代当前的药物和外科技术来使血栓性肾透析移植物再通。含有微泡的全氟化碳能够使急性冠状动脉血栓再通，并将氧气从肺部扩散到缺血组织，将结合起来确定这些特性如何改善急性冠状动脉综合征患者的临床结果。最后，将在接受电生理测试的患者中评估含有微泡的全氟化碳在低频超声存在下诱导心房和心室起搏节律的能力。这些多方面的研究将为使用微泡作为当前心血管疗法的替代或补充提供框架。拟议的商业应用：除了诊断应用之外，含有白蛋白微泡的全氟化碳还可能具有多种治疗应用。首先，它们可能是一种将特定静脉内反义寡核苷酸靶向递送至受损内皮的非侵入性方法。它们还可以将氧气输送到缺血组织。在经皮低频超声存在的情况下，它们会形成空穴并分解动脉内血栓。因此，它们可能是治疗血液透析通路移植物血栓或急性冠状动脉综合征的纤溶疗法的替代或补充。