Pandya Rachna S, Mao Lilly L J, Zhou Edward W, Bowser Robert, Zhu Zhenglun, Zhu Yongjin, Wang Xin
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Department of Neurosurgery, Boston, Massachusetts 02115, USA.
Cent Nerv Syst Agents Med Chem. 2012 Mar;12(1):15-27. doi: 10.2174/187152412800229152.
Various molecular mechanisms including apoptosis, inflammation, oxidative stress, mitochondrial dysfunction and excitotoxicity have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), though the exact mechanisms have yet to be specified. Furthermore, the underlying restorative molecular mechanisms resulting in neuronal and/or non-neuronal regeneration have to be yet elucidated. Therapeutic agents targeting one or more of these mechanisms to combat either initiation or progression of the disease are under research. Novel treatments including stem cell therapy, growth factors, and gene therapy might prolong survival and delay progression of symptoms. Harnessing the regenerative potential of the central nervous system would be a novel approach for the treatment of motor neuron death resulting from ALS. Endogenous neural replacement, if augmented with administration of exogenous growth factors or with pharmaceuticals that increase the rate of neural progenitor formation, neural migration, and neural maturation could slow the rate of cell loss enough to result in clinical improvement. In this review, we discuss the impact of therapeutic treatment involving stem cell therapy, growth factors, gene therapy, and combination therapy on disease onset and progression of ALS. In addition, we summarize human clinical trials of stem cell therapy, growth factor therapy, and gene therapy in individuals with ALS.
包括细胞凋亡、炎症、氧化应激、线粒体功能障碍和兴奋性毒性在内的多种分子机制与肌萎缩侧索硬化症（ALS）的发病机制有关，尽管确切机制尚未明确。此外，导致神经元和/或非神经元再生的潜在修复分子机制仍有待阐明。针对这些机制中的一种或多种以对抗疾病起始或进展的治疗药物正在研究中。包括干细胞疗法、生长因子和基因疗法在内的新型治疗方法可能会延长生存期并延缓症状进展。利用中枢神经系统的再生潜力将是治疗ALS导致的运动神经元死亡的一种新方法。如果通过给予外源性生长因子或使用能提高神经祖细胞形成、神经迁移和神经成熟速率的药物来增强内源性神经替代，可能会减缓细胞丢失速率，从而实现临床改善。在本综述中，我们讨论了涉及干细胞疗法、生长因子、基因疗法和联合疗法的治疗对ALS疾病起始和进展的影响。此外，我们总结了针对ALS患者的干细胞疗法、生长因子疗法和基因疗法的人体临床试验。
