PNA for Stroke

描述（由申请人提供）：中风是美国第三大死亡原因，也是严重长期残疾的主要原因。据估计，美国每年中风的总成本约为430亿美元。唯一FDA批准的治疗急性缺血性卒中的方法是重组组织纤溶酶原激活剂（rt-PA）。然而，rt-PA的治疗窗仅为卒中发作后3小时，治疗可能会增加脑出血的发生率。在过去的十多年中，数百种神经保护化合物由于其无效或高毒性而在临床试验中失败。SynZyme Technologies，LLC开发了一种新的治疗方法，多硝基化白蛋白（PNA）。PNA是通过共价标记人血清白蛋白与高摩尔比的氮氧化物，作为神经血管保护剂和有效的抗氧化剂。PNA已经在美国的一些领先的中风研究中心进行了测试，并在各种动物中风模型中显示出巨大的前景。PNA治疗的可行性不仅通过其有希望的临床前结果和良好的安全性特征得到证实，而且还通过先前涉及单独抗氧化剂或涉及单独人血白蛋白的抗氧化剂的临床试验经验得到证实。广泛的研究工作正在引导PNA进入药物开发阶段，作为急性缺血性和出血性卒中的治疗。我们于2004年5月6日收到FDA关于PNA开发的明确建议。这项拟议工作的目标是完成FDA对研究性新药（IND）申请的要求，这是新药批准的重要步骤。有三个主要组成部分完成：化学生产和控制（CMC），GLP毒性研究和临床方案制定。SynZyme的团队将管理并与高质量的认证合同研究组织（CRO）合作，以实现根据FDA的指导提出的目标。IND申请的完成将导致人体临床试验。

DESCRIPTION (provided by applicant): Stroke is the 3rd leading cause of death in the U.S. and is also a leading cause of severe, long-term disability. The total cost of stroke to the United States is estimated at about $43 billion per year. The only FDA-approved treatment for acute ischemic stroke is recombinant tissue plasminogen activator (rt- PA). However, the therapeutic window of rt-PA is only up to 3 hours from onset of stroke, and the treatment may increase the incidence of intracerebral hemorrhage. In the past decade or more, hundreds of neuroprotective compounds have failed in clinical trails due to either their insignificant effectiveness or high toxicity. SynZyme Technologies, LLC, has developed a novel therapy, polynitroxylated albumin (PNA). PNA is synthesized by covalently labeling human serum albumin with a high molar ratio of nitroxides, which act as neurovascular protectants and potent antioxidants. PNA has been tested in a number of leading stroke research centers in the U.S. and showed great promise in various animal stroke models. The feasibility of PNA treatment is confirmed not only by its promising pre-clinical results and its good safety profile, but also by previous clinical trial experience involving either antioxidants alone or those involving human albumin alone. The extensive research efforts are leading PNA into the drug development phase as a treatment of acute ischemic and hemorrhagic stroke. We received clear recommendations from the FDA on PNA development on May 6, 2004. The goal of this proposed work is to complete the requirements of the FDA for an Investigational New Drug (IND) application, an essential step to new drug approval. There are three major components for the completion: chemistry manufacturing and control (CMC), GLP toxicity studies, and clinical protocol development. SynZyme's team will manage and work with high quality certified contract research organizations (CRO) to achieve the proposed Aims according to the FDA's guidance. The completion of IND application will lead to human clinical trials.