PNA FOR STROKE

一期工程论证了开发的可行性 治疗中风的多氮氧基白蛋白(PNA)。2小时后给药 在大鼠短暂性大脑中动脉闭塞模型中，PNA通过以下方式减少平均梗塞体积 47%，与之前的鼠标数据一致。功能磁共振成像数据 表明PNA既能改善缺血区的血流灌注 在缺血期间和缺血后，并降低缺血的严重程度 受伤。PNA对大鼠脑缺血后白细胞黏附有抑制作用 肠系膜。这些发现支持一种有效的自由基阻断作用。 PNA活性，减轻缺血/再灌注损伤。这一阶段 II项目将延长PNA的临床前开发，最终 在IND提交的文件中。该项目将包括剂量反应和 毒性测试，证实在栓塞性中风模型中的有效性。 药效测试将要求(1)鉴于其在 脑缺血，PNA单独给药是否改善预后 血栓模型；和(2)给予rt-PA时，PNA是否改善预后 与单独使用rt-PA相比？第二阶段项目将测试 假设作为中风治疗的血管制剂，PNA可以起作用 单独用来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。 建议的商业应用： 该项目旨在开发用于中风治疗的PNA，以解决 缺血/再灌注损伤。这可能会产生一种药物，延长 溶栓治疗的安全性和有效性。商业潜力 这种制剂的研制将给患者带来极大的好处，并将 有很大的商业潜力。

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.