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Apyrase to Treat Ischemia/Reperfusion Injury during Lung Transplantation

三磷酸腺苷双磷酸酶治疗肺移植期间的缺血/再灌注损伤

基本信息

批准号：
7218419
负责人：
RIDONG CHEN
金额：
$ 18.96万
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：
2007-05-01 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7218419
关键词：
Adenosine Air Animals Anti-Inflammatory Agents Anti-inflammatory Antiplatelet Drugs Apyrase Binding Biological Assay Biological Markers Biological Preservation Blood Blood Platelets Blood Vessels Blood flow C-terminal Cell Line Cell surface Cells Chimeric Proteins Chinese Hamster Ovary Cell Clinic Clinical Coagulation Process Complication Computer Assisted Condition Cryopreservation Culture Media Data Dose Endothelial Cells Engineering Enzymes Exhibits Failure Fibrin Functional disorder Funding Gases Genes Goals Grant Half-Life Harvest Heart Hemorrhage Hour Human Hydrolysis Incidence Inflammation Informatics Injury Interleukin-1 Interleukin-6 Intestines Ischemia Laboratories Laboratory Research Lead Left lung Length of Stay Life Liver Lung Lung Transplantation Lung diseases Mechanical ventilation Mediating Modeling Morbidity - disease rate Mus Neutrophil Infiltration Numbers Operative Surgical Procedures Organ Outcome Patients Phase Physiological reperfusion Platelet Activation Platelet aggregation Preclinical Testing Process Production Protein Overexpression Proteins Quality of life Rattus Reperfusion Injury Reperfusion Therapy Research Risk Rodent Safety Serum Small Business Funding Mechanisms Small Business Innovation Research Grant Staging Survival Rate TNF gene Techniques Testing Therapeutic Thrombus Transplant Recipients Transplantation Treatment Protocols Universities Washington Weight base clinically relevant dosage extracellular fluidity improved in vivo inhibitor/antagonist injured intravenous administration lung preservation mortality novel prevent vector

项目摘要

DESCRIPTION (provided by applicant): Human apyrase represents a highly promising therapy to reduce ischemia/reperfusion injury which occurs in10-20% of lung transplant recipients as the consequence of unavoidable processes of procurement, preservation and restoring blood flow. This clinical condition, recently termed primary graft dysfunction, remains an important problem after lung transplantation, and still represents the single biggest cause of early morbidity and mortality for lung recipients. Apyrase strongly inhibits platelet activation and inflammation with modest bleeding risk. Using a protein informatics approach, we have successfully engineered a clot-targeting human apyrase, APT202, which exhibits significantly higher enzymatic activity and platelet inhibition than the wild-type apyrase. With the Phase I SBIR grant support, we will optimize the dose regimen of APT202 that will provide significant benefits while maintaining low bleeding risk in established animal transplantation models. The ultimate goal is to advance APT202 into clinic to improve patient outcome in terms of oxygenation improvement, reduction for duration of mechanical ventilation and hospital stay. Human apyrase represents a highly promising therapy to reduce ischemia/reperfusion injury associated with lung transplantation. We will optimize the dose regimen of a clot- targeting apyrase that will provide significant benefits while maintaining low bleeding risk in established animal transplantation models.

描述（由申请人提供）：人腺苷三磷酸双磷酸酶代表了一种非常有前途的治疗方法，可以减少缺血/再灌注损伤，缺血/再灌注损伤发生在10 -20%的肺移植受者中，是不可避免的获取、保存和恢复血流过程的结果。这种临床状况，最近被称为原发性移植物功能障碍，仍然是肺移植后的一个重要问题，并且仍然是肺受体早期发病率和死亡率的单一最大原因。腺苷三磷酸双磷酸酶强烈抑制血小板活化和炎症，具有适度的出血风险。使用蛋白质信息学方法，我们已经成功地设计了一个凝块靶向人类腺苷三磷酸双磷酸酶，APT 202，它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。在I期SBIR资助的支持下，我们将优化APT 202的剂量方案，这将在建立的动物移植模型中提供显著的益处，同时保持低出血风险。最终目标是将APT 202推进临床，以改善患者在氧合改善、减少机械通气持续时间和住院时间方面的结局。人腺苷三磷酸双磷酸酶代表了一种非常有前途的治疗方法，以减少与肺移植相关的缺血/再灌注损伤。我们将优化凝块靶向腺苷三磷酸双磷酸酶的剂量方案，这将在建立的动物移植模型中提供显著的益处，同时保持低出血风险。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Monocyte differentiation is controlled by MyD88 after mouse orthotopic lung transplantation.

小鼠原位肺移植后单核细胞分化由 MyD88 控制。

DOI：
10.1016/j.transproceed.2008.09.064
发表时间：
2009
期刊：
Transplantation proceedings
影响因子：
0.9
作者：
Sugimoto,S;Lin,X;Okazaki,M;Lai,J;Tietjens,JR;Huang,H;Patterson,GA;Krupnick,AS;Kreisel,D;Gelman,AE
通讯作者：
Gelman,AE