THERAPEUTIC APPLICATIONS OF MICROBUBBLES-PHASE II

微泡第二阶段的治疗应用

• 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
• 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

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的微泡的全氟化合物的多种治疗特性来实现非侵入性靶向靶向合成基因治疗，并重新稳固化的溶栓接入移植物和冠状动脉动脉。静脉内含有白蛋白微泡的静脉内全氟化合物结合并将反义寡核苷酸粘合到C-MYC质子核苷酸质核苷酸后，将在冠状动脉内部署后将其量化为内皮，然后进行量化，然后在人类中进行测试，以确定它是否会大大减少再萎缩症。其次，将对这些静脉微泡在存在低频超声的情况下的这些静脉微泡中微碎片动脉血栓的能力进行前瞻性评估，以确定它是否可以替代当前的药理和外科手术技术，从而在重新加以重新加持的血栓性肾脏透析透析移植物中。将合并含有微泡的全氟化合物既可以重新加固急性冠状动脉血栓形成，又将弥漫性氧气从肺部到缺血组织，以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合物在低频超声下诱导心房和心室节奏的节奏的能力。这些多面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：除了诊断应用外，包含白蛋白微泡的全氟化合物可能具有多种治疗应用。首先，它们可能是靶向特定静脉内反义寡核苷酸递送到受损的内皮细胞的无创方法。他们还可以靶向氧气递送到缺血组织。在经皮低频超声的情况下，它们会脱落并破坏动脉内血栓。因此，它们可能是治疗血液透析接纳移植血栓形成或急性冠状动脉综合征的纤维蛋白疗法的替代或补充。