Parkinson's disease (PD) is characterized by both motor and nonmotor deficits. Among cardinal symptoms of this disorder, tremor is the least responsive to dopamine replacement therapy and is often undertreated. Zuranolone (SAGE-217) is an investigational oral neuroactive steroid (NAS) gamma-aminobutyric acid A (GABAA) receptor-positive allosteric modulator (PAM) that has been investigated for its safety and efficacy in patients with PD. In the current open-label study, zuranolone capsules (20 to 30 mg) were administered for 7 days in 14 patients (mean age, 65.1 years; mean time since PD diagnosis, 9 years). The primary efficacy endpoint was reduction in tremor symptoms, as assessed by change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Tremor Scores on Day 8. Additional endpoints included improvements in overall motor symptoms, and motor and nonmotor aspects of daily living. Adverse events (AEs) were also monitored. The MDS-UPDRS Part II/III Tremor Score improved by 40% (P < 0.0001) from baseline on Day 8. The motor score, and nonmotor experiences of daily living (nM-EDL), and motor experiences of daily living (m-EDL) scores (MDS-UPDRS Parts I and II, respectively), also improved on Day 8. No serious AEs were reported, and no patients discontinued treatment. The most common AEs were dizziness, sedation, and somnolence. Zuranolone was generally well tolerated and improved tremor symptoms in patients with PD who were on stable doses of concurrent dopaminergic agents. These data support the further investigation of NAS GABAA receptor PAMs as adjunctive treatments for tremor in patients with PD.

中文翻译：

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Zuranolone 作为治疗帕金森震颤的口服辅助剂：一项 2 期开放标签研究

帕金森病 (PD) 的特点是运动和非运动缺陷。在这种疾病的主要症状中，震颤对多巴胺替代疗法的反应最差，而且往往治疗不足。Zuranolone (SAGE-217) 是一种研究性口服神经活性类固醇 (NAS) γ-氨基丁酸 A (GABAA) 受体阳性变构调节剂 (PAM)，已对其在 PD 患者中的安全性和有效性进行了研究。在目前的开放标签研究中，14 名患者（平均年龄 65.1 岁；自 PD 诊断的平均时间为 9 年）服用 Zuranolone 胶囊（20 至 30 毫克）7 天。主要疗效终点是震颤症状的减轻，根据第 8 天运动障碍协会-统一帕金森病评定量表 (MDS-UPDRS) 第 II/III 部分震颤评分相对于基线的变化进行评估。其他终点包括整体运动症状以及日常生活的运动和非运动方面的改善。还监测了不良事件 (AE)。MDS-UPDRS Part II/III 震颤评分比第 8 天的基线提高了 40% (P < 0.0001)。运动评分、日常生活的非运动体验 (nM-EDL) 和日常生活的运动体验 (m- EDL) 评分（分别为 MDS-UPDRS 第 I 部分和第 II 部分）也在第 8 天有所改善。没有报告严重的 AE，也没有患者停止治疗。最常见的 AE 是头晕、镇静和嗜睡。Zuranolone 通常耐受性良好，并改善了同时服用稳定剂量多巴胺能药物的 PD 患者的震颤症状。这些数据支持进一步研究 NAS GABAA 受体 PAM 作为 PD 患者震颤的辅助治疗。