将塞来昔布作为帕金森病患者辅助治疗的再利用：新的治疗曙光：随机对照试点研究

Repurposing celecoxib as adjuvant therapy in patients with Parkinsonian disease: a new therapeutic dawn: randomized controlled pilot study

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INFLAMMOPHARMACOLOGY

影响因子:5.3

分区:医学3区 / 毒理学2区免疫学3区

发表日期:2024 Dec

作者: Mohannad O Khrieba, Sahar K Hegazy, Wessam Mustafa, Sahar M El-Haggar

DOI: 10.1007/s10787-024-01567-z

摘要

帕金森病（PD）是一种慢性神经退行性疾病，临床表现包括运动迟缓、运动减退、僵硬、静止性震颤和姿势不稳。近年来，神经炎症被认为参与了PD的发病机制。非甾体抗炎药的应用引起关注，用于治疗这些神经炎症。为探讨塞来昔布在接受常规治疗的PD患者中的有效性，进行了一项随机、前瞻性、对照研究。共纳入60名符合PD诊断标准的门诊患者，随机分为两组（每组30例）；对照组接受标准的PD治疗（左旋多巴/卡比多巴），塞来昔布组在标准治疗基础上额外使用塞来昔布。神经科医师在治疗开始和6个月后评估每位患者，使用统一帕金森病评分量表（UPDRS）进行评估。治疗前后检测α-突触核蛋白（α-Syn）、肿瘤坏死因子α（TNF-α）、Toll样受体-4（TLR-4）、核因子红细胞相关因子2（Nrf-2）和脑源性神经营养因子（BDNF）水平。采用配对t检验和非配对t检验分别评估组内和组间的统计学差异。结果显示，塞来昔布组在TLR-4（p＝0.004）、TNF-α（p＝0.042）和α-Syn（p＝0.004）水平方面均显著下降，而BDNF（p＝0.0005）和Nrf-2（p＝0.004）水平显著升高，且UPDRS评分明显改善（p＜0.05），优于对照组。塞来昔布可能成为帕金森病管理的有潜力的辅助药物。NCT05962957。

Abstract

The clinical presentations of Parkinson's disease (PD), a chronic neurodegenerative condition, include bradykinesia, hypokinesia, stiffness, resting tremor, and postural instability. Recently, neuroinflammation is involved in pathogenesis of PD. Application of nonsteroidal anti-inflammatory drugs captured attention to treat these neuroinflammation.To investigate the possible effectiveness of celecoxib in patients with PD treated with conventional treatment.Sixty outpatients who fulfilled the inclusion requirements for PD were enrolled in this randomized, prospective, and controlled study. The patients were allocated into two groups at random (n = 30); the control group received standard PD treatment, consisting of levodopa/carbidopa, and the celecoxib group received standard PD treatment plus celecoxib. A neurologist evaluated each patient at the beginning of the treatment and after 6 months. Assessment of Unified Parkinson's disease rating scale (UPDRS) for each patient. Before and after treatment, α -synuclein (α-Syn), tumor necrosis factor alpha (TNF-α), Toll like receptors-4 (TLR-4), nuclear factor erythroid 2-related factor 2 (Nrf-2) and brain-derived neurotropic factor (BDNF) were assessed. Paired and unpaired t tests were used to assess statistical significance within and between groups respectively.The celecoxib group exhibited a significant and statistical reduction in the level of measured parameters by unpaired t test as followed: TLR-4 (p = 0.004), TNF-α (p = 0.042), and α-Syn (p = 0.004) apart from a significant increase in BDNF (p = 0.0005) and Nrf-2 (p = 0.004), in comparison with the control group. Also, UPDRS was significantly decreased in celecoxib group (p < 0.05).Celecoxib could be a promising adjuvant therapy in managing patients with PD.NCT05962957.