Pharmacologic inhibitors of PDGFR for the treatment of PVR

用于治疗 PVR 的 PDGFR 药物抑制剂

基本信息

批准号：
7344709
负责人：
Gisela Velez
金额：
$ 23.21万
依托单位：
SCHEPENS EYE RESEARCH INSTITUTE
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：
2007-02-01 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7344709
关键词：
ABL1 gene Adverse effects Applications Grants Attenuated Bcr-Abl tyrosine kinase Cataract Cells Characteristics Cicatrix Clinical Clinical Trials Complement Complex Complication Condition Development Disease Disease model Dominant-Negative Mutation Dose Drug Kinetics Epiretinal Membrane Eye Fibrosis Foundations Functional disorder Future Goals Grant Human Imatinib mesylate Incidence Inferior Institutes Intervention Knowledge Lead Macular degeneration Mentored Clinical Scientist Development Award (K08)Metabolic Clearance Rate Modeling Molecular Operative Surgical Procedures Oryctolagus cuniculus Other Therapy Patient Care Patients Pharmaceutical Preparations Philadelphia Chromosome Philadelphia Chromosome Negative Chronic Myelogenous Leukemia Platelet Inhibitors Platelet-Derived Growth Factor Platelet-Derived Growth Factor Receptor Play Poison Proliferative Vitreoretinopathy Prophylactic treatment Protein Tyrosine Kinase Proto-Oncogene Protein c-kit Randomized Clinical Trials Recovery Research Research Institute Research Personnel Retina Retinal Detachment Retinopathy of Prematurity Risk Role STI571 Schedule Scientist Specificity Standards of Weights and Measures Stem Cell Factor Structure of retinal pigment epithelium System Techniques Testing Therapeutic Time Toxic effect Training Tyrosine Kinase Inhibitor United States Food and Drug Administration Visual Vitreous Hemorrhage Work autocrine base c-abl Proto-Oncogenes career day density dosage drug clearance experience human subject improved inhibitor/antagonist injured neovascular outcome forecast prevent programs proliferative diabetic retinopathy receptor research study skills tool

项目摘要

DESCRIPTION (provided by applicant): As a recipient of a Mentored Clinical Scientist Development Award (K08) I would be able to work directly under the sponsorship of Dr. Andrius Kazlauskas at the Schepens Eye Research Institute in my goal of pursuing a career that combines patient care with research. Working and collaborating on a full-time basis with experienced scientists in an Institute known for its excellence in eye research, will allow me to acquire the basic skills necessary to further understand and investigate molecular mechanisms involved in the pathophysiology of ocular disease, and in particular proliferative vitreoretinopathy (PVR). This would complement and further expand the foundation laid by my prior training, and give me the tools needed to become a productive and significant contributor to my field through years to come. The work proposed in this grant is meant to advance our understanding PVR and the role that platelet derived growth factor (PDGF) plays in this disease. More importantly, allow us to search for potential agents for the treatment of this blinding condition in humans. To this end, this proposal focuses on studying the efficacy and toxicity of STI571, a PDGFR inhibitor, in a rabbit model of PVR. Other agents will also be tested and compared as they become available. The results from this work could potentially lead to future clinical trials that could change how we treat this disease in humans, and improve the prognosis for visual recovery for patients who develop this potentially blinding complication. Furthermore, the knowledge acquired through this work could lead to increased understanding of and future therapies for other blinding intraocular disorders involving fibrous proliferation, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and subretinal fibrosis and disciform scar formation such as seen in macular degeneration (AMD).

描述（由申请人提供）：作为指导临床科学家发展奖 (K08) 的获得者，我将能够直接在 Schepens 眼科研究所 Andrius Kazlauskas 博士的赞助下工作，我的目标是追求结合患者护理与研究。在以卓越的眼科研究而闻名的研究所中与经验丰富的科学家进行全职工作和合作，将使我获得进一步了解和研究眼部疾病病理生理学所涉及的分子机制所需的基本技能，特别是增殖性玻璃体视网膜病变（PVR）。这将补充并进一步扩展我之前的培训所奠定的基础，并为我提供所需的工具，使我在未来几年成为我的领域的富有成效和重要的贡献者。这笔资助中提出的工作旨在加深我们对 PVR 以及血小板衍生生长因子 (PDGF) 在这种疾病中所起作用的理解。更重要的是，让我们能够寻找治疗人类这种致盲疾病的潜在药物。为此，本提案重点研究PDGFR抑制剂STI571在兔PVR模型中的功效和毒性。其他代理也将在可用时进行测试和比较。这项工作的结果可能会导致未来的临床试验，从而改变我们治疗人类这种疾病的方式，并改善出现这种潜在致盲并发症的患者的视力恢复预后。此外，通过这项工作获得的知识可能会增加对涉及纤维增殖的其他致盲眼内疾病的了解和未来的治疗方法，例如早产儿视网膜病变（ROP）、增殖性糖尿病视网膜病变（PDR）以及视网膜下纤维化和盘状疤痕形成等如黄斑变性 (AMD) 中所见。