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Combination Treatment of tPA and Apyrase for Stroke

tPA 和腺苷三磷酸双磷酸酶联合治疗中风

基本信息

批准号：
7904542
负责人：
RIDONG CHEN
金额：
$ 61.22万
依托单位：
APT THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7904542
关键词：
Acute Affect Agreement Alteplase Animals Antiplatelet Drugs Apyrase Aspirin Binding Proteins Blood Platelets Cause of Death Cell Culture Techniques Cell Line Cell surface Cells Cerebral hemisphere hemorrhage Cerebrum Chinese Hamster Ovary Cell Coagulation Process Complementary therapies Computer Assisted Country Culture Media Data Dose Effectiveness Elderly Endotoxins Engineering Ensure Exhibits Generations Genes Grant Guidelines Hemorrhage Human Hydrolysis Inbred SHR Rats Industry Infarction Informatics Investigational New Drug Application Ischemia Ischemic Stroke Laboratories Licensing Lilly brand of abciximab Long-Term Effects Lung Transplantation Metastatic Neoplasm to the Bone Modeling Nervous System Physiology Neurologic Patients Phase Phase I Clinical Trials Phospholipids Platelet Glycoprotein GPIIb-IIIa Complex Preclinical Testing Process Production Proteinase-Activated Receptors Proteins Protocols documentation Rattus Recovery Regimen Reporting Risk Safety Serine Serum Solutions Stroke Surface Suspension Culture System Texas Therapeutic Thrombin Time Toxic effect Universities Validation abciximab annexin A5 clinically relevant design disability effective therapy efficacy testing immunogenicity improved large scale production nonhuman primate novel percutaneous coronary intervention phase 1 study pre-clinical prevent prothrombinase complex public health relevance research study stroke therapy thrombolysis vector

项目摘要

DESCRIPTION (provided by applicant): Human apyrase represents a highly promising therapy for acute ischemic stroke which is a leading cause of death and disability with almost no effective therapy for most patients. Using a protein informatics approach, we have successfully engineered a human apyrase which exhibits significantly higher enzymatic activity and platelet inhibition than the wild-type apyrases. Importantly, the optimized apyrase conferred cerebroprotection against experimental stroke while preventing intracerebral hemorrhage. With the Phase II grant support, we will determine whether apyrase therapy is more effective while having lower bleeding risk than aspirin and a GPIIb/IIIa receptor antagonist, in combination with r-tPA for thrombolysis of stroke occlusion. PUBLIC HEALTH RELEVANCE: We will utilize clinically relevant embolic stroke models in rats to validate whether human apyrase improves efficacy and reduce cerebral hemorrhage associated with thrombolytic treatment of ischemic stroke.

描述（由申请人提供）：人腺苷三磷酸双磷酸酶是治疗急性缺血性卒中的一种非常有前途的疗法，急性缺血性卒中是导致死亡和残疾的主要原因，对大多数患者几乎没有有效的疗法。使用蛋白质信息学方法，我们已经成功地设计了一个人腺苷三磷酸双磷酸酶，表现出显着更高的酶活性和血小板抑制比野生型腺苷三磷酸双磷酸酶。重要的是，优化的腺苷三磷酸双磷酸酶在预防脑出血的同时，对实验性中风提供了显著的保护。在II期资助的支持下，我们将确定腺苷三磷酸双磷酸酶治疗是否比阿司匹林和GPIIb/IIIa受体拮抗剂联合r-tPA溶栓治疗卒中闭塞更有效，同时出血风险更低。公共卫生关系：我们将在大鼠中利用临床相关的栓塞性卒中模型来验证人腺苷三磷酸双磷酸酶是否提高了疗效并减少了与缺血性卒中的溶栓治疗相关的脑出血。