A new class of wet AMD therapeutics

新型湿性 AMD 疗法

• 批准号: 10691697
• 负责人: Elizabeth Moran
• 金额: $ 39.13万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10691697
• 关键词: Acetates; Acetone; Adoptive Transfer; Affect; Age; Age related macular degeneration; Animals; Anti-Inflammatory Agents; Antiinflammatory Effect; Basic Science; Benchmarking; Binding; Biological Assay; Blindness; Blood Circulation; Cadaver; Cell Respiration; Cells; Choroid; Choroidal Neovascularization; Clinical Research; Complication; Conditioned Culture Media; Conflict (Psychology); Coupled; Data; Disease; Economically Deprived Population; Elderly; Endothelial Cells; Exudative age-related macular degeneration; Eye; Fatty Acids; Foundations; G-Protein-Coupled Receptors; Genes; Genetic Polymorphism; Glycolysis; Immune; In Vitro; Incidence; Inflammation; Inflammatory; Intervention; Invaded; Ketone Bodies; Ketones; Ketosis; Kinetics; Knowledge; Lasers; Lead; Left; Lesion; Link; Liver; Metabolic; Metabolism; Microglia; Modeling; Mus; Natural Immunity; Oxides; Pathology; Patient Noncompliance; Patients; Phenotype; Play; Population; Process; Retina; Risk; Role; Severities; Testing; Therapeutic; Time; Treatment Efficacy; Underserved Population; VLDL receptor; Vision; Work; angiogenesis; beta-Hydroxybutyrate; bevacizumab; cell type; cost; dietary; druggable target; genome wide association study; health care delivery; health disparity; immunoregulation; legally blind; macrophage; macula; neovascularization; neutrophil; new therapeutic target; preservation; recruit; single-cell RNA sequencing; standard of care; therapy development

ABSTRACT Advanced neovascular age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV), in which neovessels originating from the choroid invade the macula. CNV causes permanent central blindness if left untreated and is the most sight-threatening pathology of AMD. The present application will investigate the efficacy and regulatory mechanisms for a new class of CNV therapeutics. Anti- VEGF therapies are the standard of care for CNV and can preserve central vision if administered on an indefinitely recurring basis but have reached their therapeutic threshold. Moreover, these therapies are costly and must be injected intravitreally, increasing the risk of complications and patient noncompliance, and limiting availability of treatment to economically disadvantaged patients affected by disparities in health care delivery. The present application has the potential to identify new therapeutics and druggable targets for CNV, particularly those that can be administered systemically rather than intravitreally, and are thus more accessible to underserved populations.

摘要 晚期新生血管性年龄相关性黄斑变性（AMD）的特征在于脉络膜视网膜病变。 新血管形成（CNV），其中源自脉络膜的新血管侵入黄斑。CNV原因 如果不进行治疗，可能会导致永久性中央失明，并且是AMD最具视力威胁的病理学。本 该申请将研究一类新的CNV治疗剂的功效和调节机制。反 VEGF疗法是CNV的护理标准，并且如果在治疗期间施用，则可以保护中心视力。 无限期复发的基础上，但已达到其治疗阈值。此外，这些疗法成本高昂 并且必须玻璃体内注射，增加了并发症和患者不依从的风险，并且限制了 向受保健服务不平等影响的经济上处于不利地位的病人提供治疗。 本申请具有鉴定CNV的新治疗剂和可药物化靶点的潜力， 特别是那些可以全身给药而不是玻璃体内给药的药物， to underserved不足populations人口.