Evaluation of Dextromethorphan as a Microglia Inhibitor in the treatment of DME

右美沙芬作为小胶质细胞抑制剂治疗 DME 的评价

• 批准号: 10020016
• 负责人: Catherine Cukras
• 金额: $ 3.03万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10020016
• 关键词: Angiography; Blindness; Blood Pressure; Blood Vessels; Cells; Chronic; Clinical Trials; Creatinine; Dextromethorphan; Diabetic Retinopathy; Enrollment; Evaluation; Extravasation; Eye; Fluorescein; Glycosylated hemoglobin A; Immune; Inflammation; Inflammation Mediators; Inflammatory; Letters; Mediation; Methods; Microglia; Neurons; Oral; Outcome; Participant; Pharmaceutical Preparations; Phase; Process; Retina; Retinal; Safety; Site; Therapeutic; Therapeutic Effect; Thick; United States; Vascular Permeabilities; Visual Acuity; cellular targeting; diabetic; improved; inhibitor/antagonist; laser photocoagulation; macula; macular edema; open label; primary endpoint; prospective

Purpose: The activation of microglia, the primary innate immune cell resident in the retina, produces inflammatory mediators, which underlie changes in diabetic retinopathy including increased vascular permeability. This study evaluates the safety and efficacy of dextromethorphan, a drug capable of inhibiting microglial activation, in the treatment of diabetic macular edema (DME). Methods: A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with macular involving DME who received oral dextromethorphan 60 mg twice daily for 6 months as monotherapy. Main outcome variables included central retinal subfield thickness (CST), best-corrected visual acuity (BCVA), macula sensitivity, and late leakage on fluorescein angiogram (FA). Results: The study drug was well tolerated. At the primary end point of 6 months, mean CST decreased by -6.3% 6.8% and BCVA increased by +0.6 5.11 (mean SEM) letters. Late leakage on FA was scored as improved in four of five study eyes. These findings were not correlated with changes in hemoglobin A1c (HbA1c), creatinine, or blood pressure. Conclusions: In this proof-of-concept study, dextromethorphan administration as the primary treatment for DME was associated with decreased vascular leakage, suggesting possible therapeutic effects. Additional studies investigating the modulation of microglial activation is warranted. Translational Relevance: These findings highlight microglial modulation as a potentially useful therapeutic strategy in the treatment of diabetic macular edema.

目的： 小胶质细胞的激活是视网膜中驻留的主要先天免疫细胞，会产生炎症介质，这是糖尿病性视网膜病变的变化，包括增加血管通透性。这项研究评估了一种能够抑制小胶质激活的药物右美甲苯克的安全性和功效，该药物在治疗糖尿病黄斑水肿（DME）方面。 方法： 一项单中心，前瞻性，开放标签期I/II临床试验招募了五名具有黄斑的参与者，涉及DME，他们每天两次接受口服右美甲芬60毫克，持续6个月，为单一治疗。主要结局变量包括中央视网膜亚场厚度（CST），最校正的视力（BCVA），黄斑敏感性以及荧光素血管造影（FA）上的晚期泄漏。 结果： 研究药物的耐受性很好。在6个月的主要终点上，平均CST降低-6.3％6.8％，BCVA增加+0.6 5.11（平均SEM）字母。在五只研究眼中的四个研究中，FA上的晚期泄漏得到了改善。这些发现与血红蛋白A1C（HBA1C），肌酐或血压的变化无关。 结论： 在这项概念验证的研究中，右美甲苯甲酸作为DME的主要治疗方法与血管泄漏的减少有关，表明可能的治疗作用。有必要研究小胶质激活调节的其他研究。 翻译相关性： 这些发现突出了小胶质细胞调制是一种在治疗糖尿病黄斑水肿的潜在有用的治疗策略。