线粒体疾病的临床试验进展
Clinical trials in mitochondrial disorders, an update.
机构信息
Section of Medical Genetics, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
出版信息
Mol Genet Metab. 2020 Sep-Oct;131(1-2):1-13. doi: 10.1016/j.ymgme.2020.10.002. Epub 2020 Oct 6.
Abstract
Mitochondrial disorders comprise a molecular and clinically diverse group of diseases that are associated with mitochondrial dysfunction leading to multi-organ disease. With recent advances in molecular technologies, the understanding of the pathomechanisms of a growing list of mitochondrial disorders has been greatly expanded. However, the therapeutic approaches for mitochondrial disorders have lagged behind with treatment options limited mainly to symptom specific therapies and supportive measures. There is an increasing number of clinical trials in mitochondrial disorders aiming for more specific and effective therapies. This review will cover different treatment modalities currently used in mitochondrial disorders, focusing on recent and ongoing clinical trials.
摘要
线粒体疾病包括一组分子和临床表现多样的疾病，这些疾病与线粒体功能障碍有关，导致多器官疾病。随着分子技术的最新进展，对越来越多的线粒体疾病的病理机制的理解有了很大的扩展。然而，线粒体疾病的治疗方法却落后了，治疗方法主要局限于针对特定症状的治疗和支持性措施。目前有越来越多的线粒体疾病临床试验旨在寻求更具体和有效的治疗方法。本文将综述目前用于线粒体疾病的不同治疗方式，重点介绍最近和正在进行的临床试验。
相似文献
1
Clinical trials in mitochondrial disorders, an update.线粒体疾病的临床试验进展
Mol Genet Metab. 2020 Sep-Oct;131(1-2):1-13. doi: 10.1016/j.ymgme.2020.10.002. Epub 2020 Oct 6.
2
Mitochondrial biogenesis: pharmacological approaches.线粒体生物合成：药理学方法。
Curr Pharm Des. 2014;20(35):5507-9. doi: 10.2174/138161282035140911142118.
3
Therapies for mitochondrial diseases and current clinical trials.线粒体疾病的治疗方法和当前的临床试验。
Mol Genet Metab. 2017 Nov;122(3):1-9. doi: 10.1016/j.ymgme.2017.09.009. Epub 2017 Sep 18.
4
Development of pharmacological strategies for mitochondrial disorders.线粒体疾病药理学策略的发展
Br J Pharmacol. 2014 Apr;171(8):1798-817. doi: 10.1111/bph.12456.
5
Toward a therapy for mitochondrial disease.迈向线粒体疾病的治疗方法。
Biochem Soc Trans. 2016 Oct 15;44(5):1483-1490. doi: 10.1042/BST20160085.
6
Emerging therapies for mitochondrial diseases.线粒体疾病的新兴疗法。
Essays Biochem. 2018 Jul 20;62(3):467-481. doi: 10.1042/EBC20170114.
7
Mitochondrial diseases: Drosophila melanogaster as a model to evaluate potential therapeutics.线粒体疾病：以黑腹果蝇为模型评估潜在疗法
Int J Biochem Cell Biol. 2015 Jun;63:60-5. doi: 10.1016/j.biocel.2015.01.024. Epub 2015 Feb 7.
8
Moving towards clinical trials for mitochondrial diseases.迈向线粒体疾病临床试验。
J Inherit Metab Dis. 2021 Jan;44(1):22-41. doi: 10.1002/jimd.12281. Epub 2020 Sep 2.
9
Therapies in inborn errors of oxidative metabolism.氧化代谢先天性错误的治疗方法。
Trends Endocrinol Metab. 2012 Sep;23(9):488-95. doi: 10.1016/j.tem.2012.04.006. Epub 2012 May 25.
10
Towards a therapy for mitochondrial disease: an update.迈向线粒体疾病治疗的新进展
Biochem Soc Trans. 2018 Oct 19;46(5):1247-1261. doi: 10.1042/BST20180134. Epub 2018 Oct 8.
引用本文的文献
1
Efficacy and Safety of 5-Aminolevulinic Acid Hydrochloride Combined with Sodium Ferrous Citrate in Pediatric Patients with Leigh Syndrome and Central Nervous System Disorders: An Initial Exploratory Trial with a Double-Blind Placebo-Controlled Period, Followed by an Open-Label Period and a Subsequent Long-Term Administration Study.盐酸5-氨基酮戊酸联合柠檬酸亚铁钠治疗儿童 Leigh 综合征和中枢神经系统疾病的疗效与安全性：一项初始探索性试验，包括双盲安慰剂对照期、开放标签期及随后的长期给药研究。
Life (Basel). 2025 Jul 23;15(8):1168. doi: 10.3390/life15081168.
2
Mitochondrial cardiomyopathies: navigating through different clinical and management pictures between adult and paediatric forms.线粒体心肌病：梳理成人和儿童形式之间不同的临床及管理情况。
Front Cardiovasc Med. 2025 Jul 3;12:1621096. doi: 10.3389/fcvm.2025.1621096. eCollection 2025.
3
The treatment of primary CoQ deficiency requires the targeting of multiple pathogenic mechanisms.原发性辅酶Q缺乏症的治疗需要针对多种致病机制。
Commun Med (Lond). 2025 Jul 10;5(1):286. doi: 10.1038/s43856-025-01000-8.
4
Mitochondrial DNA depletion syndrome and its cardiac complication.线粒体DNA耗竭综合征及其心脏并发症。
Front Cardiovasc Med. 2025 Jun 10;12:1582219. doi: 10.3389/fcvm.2025.1582219. eCollection 2025.
5
Role of mitochondria in physiological activities, diseases, and therapy.线粒体在生理活动、疾病及治疗中的作用。
Mol Biomed. 2025 Jun 19;6(1):42. doi: 10.1186/s43556-025-00284-5.
6
Mitochondrial quality control in cardiomyocytes: safeguarding the heart against disease and ageing.心肌细胞中的线粒体质量控制：保护心脏免受疾病和衰老影响。
Nat Rev Cardiol. 2025 Mar 20. doi: 10.1038/s41569-025-01142-1.
7
Therapeutic Approach to Epilepsy in Patients with Mitochondrial Diseases.线粒体疾病患者癫痫的治疗方法
Yonsei Med J. 2025 Mar;66(3):131-140. doi: 10.3349/ymj.2024.0325.
8
Atomic vacancies of molybdenum disulfide nanoparticles stimulate mitochondrial biogenesis.二硫化钼纳米颗粒中的原子空位会刺激线粒体生物发生。
Nat Commun. 2024 Sep 17;15(1):8136. doi: 10.1038/s41467-024-52276-8.
9
mTOR signaling is required for phagocyte free radical production, GLUT1 expression, and control of infection.mTOR 信号通路对于吞噬细胞产生自由基、GLUT1 表达以及控制感染是必需的。
mBio. 2024 Jun 12;15(6):e0086224. doi: 10.1128/mbio.00862-24. Epub 2024 May 20.
10
Exercise Improves Heart Function after Myocardial Infarction: The Merits of AMPK.运动改善心肌梗死后的心功能：AMPK的益处
Cardiovasc Drugs Ther. 2024 Mar 4. doi: 10.1007/s10557-024-07564-2.
本文引用的文献
1
The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans.自噬激活剂尿石素 A 安全无毒，可诱导人体线粒体和细胞健康的分子特征改善。
Nat Metab. 2019 Jun;1(6):595-603. doi: 10.1038/s42255-019-0073-4. Epub 2019 Jun 14.
2
Therapeutic Manipulation of mtDNA Heteroplasmy: A Shifting Perspective.线粒体DNA异质性的治疗性调控：视角转变
Trends Mol Med. 2020 Jul;26(7):698-709. doi: 10.1016/j.molmed.2020.02.006. Epub 2020 Mar 26.
3
Niacin Cures Systemic NAD Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy.烟酰胺可治疗系统性 NAD 缺乏症，并改善成年起病的线粒体肌病患者的肌肉性能。
Cell Metab. 2020 Jun 2;31(6):1078-1090.e5. doi: 10.1016/j.cmet.2020.04.008. Epub 2020 May 7.
4
Mitochondrial diseases in North America: An analysis of the NAMDC Registry.北美地区的线粒体疾病：北美线粒体疾病协作组登记处分析
Neurol Genet. 2020 Mar 2;6(2):e402. doi: 10.1212/NXG.0000000000000402. eCollection 2020 Apr.
5
Mitochondrial Diseases: Hope for the Future.线粒体疾病：未来的希望。
Cell. 2020 Apr 2;181(1):168-188. doi: 10.1016/j.cell.2020.02.051. Epub 2020 Mar 26.
6
Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).成功进行线粒体神经胃肠脑肌病（MNGIE）肝移植。
Mol Genet Metab. 2020 May;130(1):58-64. doi: 10.1016/j.ymgme.2020.03.001. Epub 2020 Mar 6.
7
Endothelial Dysfunction and the Effect of Arginine and Citrulline Supplementation in Children and Adolescents With Mitochondrial Diseases.内皮功能障碍以及补充精氨酸和瓜氨酸对线粒体疾病儿童和青少年的影响。
J Cent Nerv Syst Dis. 2020 Feb 29;12:1179573520909377. doi: 10.1177/1179573520909377. eCollection 2020.
8
The special considerations of gene therapy for mitochondrial diseases.线粒体疾病基因治疗的特殊考量
NPJ Genom Med. 2020 Mar 2;5:7. doi: 10.1038/s41525-020-0116-5. eCollection 2020.
9
Metabolic effects of bezafibrate in mitochondrial disease.苯扎贝特在线粒体疾病中的代谢作用。
EMBO Mol Med. 2020 Mar 6;12(3):e11589. doi: 10.15252/emmm.201911589. Epub 2020 Feb 28.
10
Bezafibrate Improves Mitochondrial Fission and Function in DNM1L-Deficient Patient Cells.贝扎贝特可改善 DNM1L 缺陷患者细胞中的线粒体裂变和功能。
Cells. 2020 Jan 27;9(2):301. doi: 10.3390/cells9020301.
Zotero 插件