PNA FOR STROKE

第一阶段项目证明了发展的可行性， 多硝酰白蛋白（PNA）治疗中风。 给药后2小时 短暂MCA闭塞大鼠，PNA减少平均梗死体积， 47%，与之前的小鼠数据一致。 功能性MRI数据 表明PNA既能改善缺血区的灌注， 在缺血期间和之后，并降低缺血的严重性， 损伤 PNA还能抑制大鼠缺血后白细胞粘附 肠系膜 这些发现支持了一种有效的自由基阻断剂 PNA的活性，其减轻缺血/再灌注损伤。 相位 II项目将扩展PNA的临床前开发， 在IND申请中。 该项目将包括剂量反应和 毒性测试，在栓塞性中风模型中的功效确认。 有效性试验将询问（1）鉴于其在以下情况下的血流动力学效应： 在缺血性脑中，PNA单独给药是否能改善预后？ 栓塞模型;（2）当给予rt-PA时，PNA是否改善结局 与单独使用rt-PA相比？ 第二阶段项目将测试 假设作为中风治疗血管剂，PNA可以 单独抑制中风损伤的进展，也可以改善 溶栓治疗的安全性和有效性。 拟定商业应用： 该项目旨在开发用于中风治疗的PNA， 缺血/再灌注损伤 这可能会产生一种药物， 安全性和有效性。的商业潜力 这种药物对患者有巨大的好处， 具有巨大的商业潜力。

The Phase I project demonstrated the feasibility of developing polynitroxyl albumin (PNA) for stroke. When administered 2 hrs after transient MCA occlusion in the rat, PNA reduced mean infarct volume by 47 percent, consistent with previous mouse data. Functional MRI data indicated that PNA both improves the perfusion of the ischemic area during and after ischemia, and reduces the severity of the ischemic injury. PNA also inhibited postischemic leukocyte adhesion in the rat mesentery. These findings support a potent free radical blocking activity of PNA which attenuates ischemia/reperfusion injury. The Phase II project will extend the preclinical development of PNA, culminating in an IND submission. The project will include dose-response and toxicity testing, confirmation of efficacy in embolic stroke models. The efficacy testing will ask (1) in view of its hemodynamic effects in the ischemic brain, does PNA improve outcome when given alone in an embolic model; and (2) when given with rt-PA, does PNA improve outcome compared with rt-PA alone? The Phase II project will test the hypothesis that as a vascular agent for stroke therapy, PNA can act alone to inhibit the progression of stroke injury, and can also improve the safety and efficacy of thrombolytic therapy. PROPOSED COMMERCIAL APPLICATION: The project aims to develop PNA for stroke therapy which addresses ischemia/reperfusion injury. This may yield a drug which extend the safety and efficacy of thrombolytic therapy. The commercial potential of such an agent would be of tremendous benefit to patients and would have great commercial potential.