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： 小胶质细胞是视网膜中的主要先天免疫细胞，其激活会产生炎症介质，这是糖尿病视网膜病变变化的基础，包括血管通透性增加。本研究评估了右美沙芬（一种能够抑制小胶质细胞活化的药物）治疗糖尿病性黄斑水肿（DME）的安全性和有效性。 方法： 一项单中心、前瞻性、开放标签 I/II 期临床试验招募了 5 名患有黄斑 DME 的受试者，他们接受口服右美沙芬 60 mg，每天两次，为期 6 个月的单一疗法。主要结果变量包括中央视网膜亚区厚度（CST）、最佳矫正视力（BCVA）、黄斑敏感性和荧光素血管造影（FA）的晚期渗漏。 结果： 研究药物耐受性良好。在 6 个月的主要终点，平均 CST 下降了 -6.3% ~ 6.8%，BCVA 增加了 +0.6 ~ 5.11（平均 SEM）字母。五只研究眼中有四只眼睛的 FA 晚期渗漏评分为改善。这些发现与糖化血红蛋白 (HbA1c)、肌酐或血压的变化无关。 结论： 在这项概念验证研究中，右美沙芬作为 DME 的主要治疗方法与血管渗漏减少相关，这表明可能的治疗效果。有必要进行更多研究来调查小胶质细胞激活的调节。 翻译相关性： 这些发现强调小胶质细胞调节作为治疗糖尿病黄斑水肿的潜在有用的治疗策略。