Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis.
Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis.
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DOI：
10.1111/ene.12664
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发表时间：
2016-01
影响因子：
5.1
通讯作者：
Albanese A
中科院分区：
文献类型：
--
作者：
Elia AE;Lalli S;Monsurrò MR;Sagnelli A;Taiello AC;Reggiori B;La Bella V;Tedeschi G;Albanese A
牛磺熊去氧胆酸 (TUDCA) 是一种亲水性胆汁酸，在肝脏中产生，用于治疗慢性胆汁淤积性肝病。实验研究表明 TUDCA 可能具有细胞保护和抗凋亡作用，并具有潜在的神经保护活性。采用原理证明方法来提供有关 TUDCA 在一系列肌萎缩侧索硬化症 (ALS) 患者中的疗效和耐受性的初步数据。作为原理证明，采用双盲安慰剂对照设计，34 名接受利鲁唑治疗的 ALS 患者被随机分配至安慰剂或 TUDCA（每次 1 g，每日两次，持续 54 周），并在 3 个月的导入期后进行评估。患者每 6 周接受一次检查。主要结局是应答者的比例[与导入阶段相比，治疗期间肌萎缩侧索硬化症功能评定量表修订版 (ALSFRS-R) 斜率改善至少 15% 的受试者]。次要结局包括研究结束时 ALSFRS-R 的治疗间比较、ALSFRS-R 平均评分的线性回归斜率比较和不良事件的发生。牛磺熊去氧胆酸耐受性良好；不良事件没有组间差异。 TUDCA 治疗组的应答者比例 (87%) 高于安慰剂治疗组 (P = 0.021；43%)。在研究结束时，TUDCA 组经基线调整的 ALSFRS-R 显着高于安慰剂组 (P = 0.007)。回归分析斜率比较显示，TUDCA 的进展速度比安慰剂组慢（P < 0.01）。该试点研究提供了初步临床数据，表明 TUDCA 是安全的，并且可能对 ALS 有效。单击此处查看本期的随附论文。
Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid that is produced in the liver and used for treatment of chronic cholestatic liver diseases. Experimental studies suggest that TUDCA may have cytoprotective and anti‐apoptotic action, with potential neuroprotective activity. A proof of principle approach was adopted to provide preliminary data regarding the efficacy and tolerability of TUDCA in a series of patients with amyotrophic lateral sclerosis (ALS). As a proof of principle, using a double‐blind placebo controlled design, 34 ALS patients under treatment with riluzole who were randomized to placebo or TUDCA (1 g twice daily for 54 weeks) were evaluated after a lead‐in period of 3 months. The patients were examined every 6 weeks. The primary outcome was the proportion of responders [those subjects with improvement of at least 15% in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS‐R) slope during the treatment period compared to the lead‐in phase]. Secondary outcomes included between‐treatment comparison of ALSFRS‐R at study end, comparison of the linear regression slopes for ALSFFRS‐R mean scores and the occurrence of adverse events. Tauroursodeoxycholic acid was well tolerated; there were no between‐group differences for adverse events. The proportion of responders was higher under TUDCA (87%) than under placebo (P = 0.021; 43%). At study end baseline‐adjusted ALSFRS‐R was significantly higher (P = 0.007) in TUDCA than in placebo groups. Comparison of the slopes of regression analysis showed slower progression in the TUDCA than in the placebo group (P < 0.01). This pilot study provides preliminary clinical data indicating that TUDCA is safe and may be effective in ALS. Click here to view the accompanying paper in this issue.
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作者：
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通讯作者：
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DOI：
10.3109/21678421.2013.778554
发表时间：
2013-05
影响因子：
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通讯作者：
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