PNA for Stroke

描述（由申请人提供）：中风是美国第三大死亡原因，也是导致严重、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。fda唯一批准的治疗急性缺血性卒中的药物是重组组织型纤溶酶原激活剂（rt- PA）。然而，rt-PA的治疗窗口期仅为脑卒中发病后3小时，治疗可能增加脑出血的发生率。在过去的十年或更长的时间里，数以百计的神经保护化合物在临床试验中失败，因为它们的有效性微不足道或高毒性。SynZyme Technologies， LLC开发了一种新的治疗方法，多硝基化白蛋白（PNA）。PNA是用高摩尔比的一氧化氮共价标记人血清白蛋白合成的，一氧化氮作为神经血管保护剂和有效的抗氧化剂。PNA已经在美国许多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很大的希望。PNA治疗的可行性不仅被其有希望的临床前结果和良好的安全性所证实，而且还被先前单独使用抗氧化剂或单独使用人类白蛋白的临床试验经验所证实。广泛的研究工作正在将PNA作为治疗急性缺血性和出血性中风的药物开发阶段。2004年5月6日，我们收到了FDA关于PNA发展的明确建议。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：化学制造和控制（CMC）， GLP毒性研究和临床方案的制定。SynZyme团队将管理并与高质量认证合同研究组织（CRO）合作，根据FDA的指导方针实现拟议的目标。IND申请完成后将进行人体临床试验。

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.