Pharmacologic inhibitors of PDGFR for the treatment of PVR

用于治疗 PVR 的 PDGFR 药物抑制剂

• 批准号: 8018062
• 负责人: Gisela Velez
• 金额: $ 2.77万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8018062
• 关键词: ABL1 gene; Adverse effects; Applications Grants; Attenuated; Bcr-Abl tyrosine kinase; Cataract; Cells; Characteristics; Cicatrix; Clinical; Clinical Trials; Complement; Complex; Complication; Development; Disease; Disease model; Dominant-Negative Mutation; Dose; Drug Kinetics; Epiretinal Membrane; Eye; FDA approved; 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; Patient Care; Patients; Pharmaceutical Preparations; Philadelphia Chromosome; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; 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; Role; STI571; Schedule; Scientist; Specificity; Stem Cell Factor; Structure of retinal pigment epithelium; System; Techniques; Testing; Therapeutic; Time; Toxic effect; Training; Tyrosine Kinase Inhibitor; Visual; Vitreous Hemorrhage; Work; autocrine; base; c-abl Proto-Oncogenes; career; density; dosage; drug clearance; efficacy testing; experience; high risk; human subject; improved; inhibitor/antagonist; injured; neovascular; outcome forecast; prevent; programs; proliferative diabetic retinopathy; receptor; research study; skills; tool

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，我将能够在Schepens眼科研究所的Andrius Kazlauskas博士的赞助下直接工作，我的目标是追求将患者护理与研究相结合的职业生涯。在一个以卓越的眼科研究而闻名的研究所与经验丰富的科学家全职工作和合作，将使我获得必要的基本技能，以进一步了解和研究眼部疾病，特别是增生性玻璃体视网膜病变（PVR）的病理生理学所涉及的分子机制。这将补充和进一步扩大我以前的培训奠定的基础，并给我所需的工具，成为一个富有成效的和重要的贡献者，我的领域，通过几年来。这项研究旨在促进我们对PVR的理解，以及血小板衍生生长因子（PDGF）在这种疾病中的作用。更重要的是，让我们能够寻找潜在的药物来治疗人类的这种致盲性疾病。为此，本提案重点研究PDGFR抑制剂STI571在PVR兔模型中的疗效和毒性。其他药剂也将在可获得时进行测试和比较。这项工作的结果可能会导致未来的临床试验，这些试验可能会改变我们在人类中治疗这种疾病的方式，并改善患有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导致对涉及纤维增生的其他致盲眼内疾病的理解和未来治疗，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黄斑变性（AMD）中可见的瘢痕形成。