Potential Disease-Modifying Effects of Lithium Carbonate in Niemann-Pick Disease, Type C1.
Potential Disease-Modifying Effects of Lithium Carbonate in Niemann-Pick Disease, Type C1.
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DOI：
10.3389/fphar.2021.667361
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发表时间：
2021
影响因子：
5.6
通讯作者：
Ye Z
中科院分区：
文献类型：
--
作者：
Han S;Zhang H;Yi M;Liu X;Maegawa GHB;Zou Y;Wang Q;Wu D;Ye Z
背景资料：C1型尼曼-皮克病（NP-C1）是一种罕见的常染色体隐性遗传神经退行性疾病，没有美国食品和药物管理局（FDA）批准的药物。锂已被证明对双相情感障碍、阿尔茨海默病和中风等神经系统疾病具有相当大的神经保护作用，并已在许多临床试验中进行了测试。然而，尚未研究锂对NP-C1神经退行性过程的药理学作用。本研究的目的是初步评价碳酸锂在NP-C1患者中的安全性和可行性。 研究方法：共有13名符合入选标准的诊断为NP-C1的患者每天口服300、600、900或1,200 mg锂。根据耐受性或安全性观察结果降低剂量。血浆7-酮胆固醇（7-KC）是一种新兴的NP-C1生物标志物，是主要终点。次要终点包括NPC神经系统严重程度评分（NNSS）和安全性。 结果：在入组的13例NP-C1患者（12-33岁）中，3例退出（停止门诊随访）。最后观察到的7-KC浓度的治疗后值（128 ng/ml，SEM 20）显著低于治疗前基线值（185 ng/ml，SEM 29; p = 0.001）。锂治疗后12个月时平均NNSS改善（p = 0.005）。在接受治疗的患者中观察到吞咽能力改善（p = 0.014）。在接受锂的患者中没有记录严重不良事件。 结论：锂是NP-C1患者的潜在治疗选择。需要更大规模的随机和双盲临床试验来进一步支持这一发现。 临床试验注册：ClinicalTrials.gov，NCT 03201627。
Background: Niemann-Pick disease type C1 (NP-C1) is a rare, autosomal-recessive neurodegenerative disorder with no United States Food and Drug Administration (FDA)-approved drug. Lithium has been shown to have considerable neuroprotective effects for neurological disorders such as bipolar disorder, Alzheimer’s disease and stroke and has been tested in many clinical trials. However, the pharmacological effect of lithium on NP-C1 neurodegenerative processes has not been investigated. The aim of this study was to provide an initial evaluation of the safety and feasibility of lithium carbonate in patients with NP-C1. Methods: A total of 13 patients diagnosed with NP-C1 who met the inclusion criteria received lithium orally at doses of 300, 600, 900, or 1,200 mg daily. The dose was reduced based on tolerance or safety observations. Plasma 7-ketocholesterol (7-KC), an emerging biomarker of NP-C1, was the primary endpoint. Secondary endpoints included NPC Neurological Severity Scores (NNSS) and safety. Results: Of the 13 patients with NP-C1 (12–33 years) enrolled, three withdrew (discontinuation of follow-up outpatient visits). The last observed post-treatment values of 7-KC concentrations (128 ng/ml, SEM 20) were significantly lower than pretreatment baselines values (185 ng/ml, SEM 29; p = 0.001). The mean NNSS was improved after lithium treatment at 12 months (p = 0.005). Improvement in swallowing capacity was observed in treated patients (p = 0.014). No serious adverse events were recorded in the patients receiving lithium. Conclusion: Lithium is a potential therapeutic option for NP-C1 patients. Larger randomized and double-blind clinical trials are needed to further support this finding. Clinical Trial Registration: ClinicalTrials.gov, NCT03201627.
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DOI：
10.1016/s0140-6736(17)31465-4
发表时间：
2017-10-14
期刊：
Lancet (London, England)
影响因子：
--
作者：
Ory DS;Ottinger EA;Farhat NY;King KA;Jiang X;Weissfeld L;Berry-Kravis E;Davidson CD;Bianconi S;Keener LA;Rao R;Soldatos A;Sidhu R;Walters KA;Xu X;Thurm A;Solomon B;Pavan WJ;Machielse BN;Kao M;Silber SA;McKew JC;Brewer CC;Vite CH;Walkley SU;Austin CP;Porter FD
通讯作者：
Porter FD
影响因子：
3.5
作者：
Hughes MP;Smith DA;Morris L;Fletcher C;Colaco A;Huebecker M;Tordo J;Palomar N;Massaro G;Henckaerts E;Waddington SN;Platt FM;Rahim AA
通讯作者：
Rahim AA
影响因子：
3.4
作者：
Khairova R;Pawar R;Salvadore G;Juruena MF;de Sousa RT;Soeiro-de-Souza MG;Salvador M;Zarate CA;Gattaz WF;Machado-Vieira R
通讯作者：
Machado-Vieira R
DOI：
10.1016/j.bbrc.2007.06.116
发表时间：
2007-08-31
影响因子：
3.1
作者：
Kim, Sun-Jung;Lee, Bong-Hee;Kang, Kyung-Sun
通讯作者：
Kang, Kyung-Sun
影响因子：
11.4
作者：
CADE, JFJ
通讯作者：
CADE, JFJ