Cell therapy in Huntington's disease: Taking stock of past studies to move the field forward.
Cell therapy in Huntington's disease: Taking stock of past studies to move the field forward.
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DOI：
10.1002/stem.3300
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发表时间：
2021-02
期刊：
影响因子：
5.2
通讯作者：
Rosser, Anne
中科院分区：
文献类型：
--
作者：
Bachoud-Levi, Anne-Catherine;Massart, Renaud;Rosser, Anne
亨廷顿氏病（HD）是一种罕见的遗传性神经退行性疾病，主要在成年期表现为进行性认知、行为和运动功能障碍。神经元损失主要发生在纹状体，但也扩展到其他大脑区域，特别是皮质。大多数患者在运动发作后20年左右死亡，尽管进展速度存在变异性和一些表型异质性。目前最先进的实验疗法是降低亨廷顿蛋白的策略，其中一些处于第3阶段临床试验。然而，即使这些方法是成功的，它们也不太可能适用于所有患者或在所有情况下完全停止神经细胞的持续损失。另一方面，细胞疗法具有恢复萎缩组织的潜力，因此可以提供重要的补充治疗途径。21世纪初的胎儿细胞移植的初步研究报告了这种疾病迄今为止取得的最显着的临床改善，但随后的研究迄今未能确定可靠重现这些结果的方法。展望未来，一个主要的挑战将是从（非胎儿）细胞来源产生合适的供体细胞，但同时也有许多程序和试验设计问题，这些问题对于提高移植的可靠性至关重要，因此迫切需要关注。在这里，我们考虑了迄今为止在HD临床移植研究中出现的发现，特别是最近多中心脑内移植HD研究中出现的新发现，并考虑如何使用这些数据为未来的细胞治疗试验提供信息。概述了解决当前生物学和临床挑战所需的迭代过程，以提高未来亨廷顿病细胞治疗试验的可靠性。
Huntington's disease (HD) is a rare inherited neurodegenerative disease that manifests mostly in adulthood with progressive cognitive, behavioral, and motor dysfunction. Neuronal loss occurs predominantly in the striatum but also extends to other brain regions, notably the cortex. Most patients die around 20 years after motor onset, although there is variability in the rate of progression and some phenotypic heterogeneity. The most advanced experimental therapies currently are huntingtin‐lowering strategies, some of which are in stage 3 clinical trials. However, even if these approaches are successful, it is unlikely that they will be applicable to all patients or will completely halt continued loss of neural cells in all cases. On the other hand, cellular therapies have the potential to restore atrophied tissues and may therefore provide an important complementary therapeutic avenue. Pilot studies of fetal cell grafts in the 2000s reported the most dramatic clinical improvements yet achieved for this disease, but subsequent studies have so far failed to identify methodology to reliably reproduce these results. Moving forward, a major challenge will be to generate suitable donor cells from (nonfetal) cell sources, but in parallel there are a host of procedural and trial design issues that will be important for improving reliability of transplants and so urgently need attention. Here, we consider findings that have emerged from clinical transplant studies in HD to date, in particular new findings emerging from the recent multicenter intracerebral transplant HD study, and consider how these data may be used to inform future cell therapy trials. An overview of the iterative process needed to address current biological and clinical challenges in order to improve reliability of future cell therapy trials in Huntington's disease.
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影响因子：
11.1
作者：
Ciosi, Marc;Maxwell, Alastair;Monckton, Darren G.
通讯作者：
Monckton, Darren G.
DOI：
10.1007/7854_2013_245
发表时间：
2015-01-01
期刊：
BEHAVIORAL NEUROBIOLOGY OF HUNTINGTON'S DISEASE AND PARKINSON'S DISEASE
影响因子：
--
作者：
Carreira, Joao Casaca;Jahanshahi, Ali;Temel, Yasin
通讯作者：
Temel, Yasin
影响因子：
16.6
作者：
Badin, Romina Aron;Bugi, Aurore;Perrier, Anselme L.
通讯作者：
Perrier, Anselme L.
影响因子：
6.9
作者：
Andrews, S. C.;Langbehn, D. R.;Stout, J. C.
通讯作者：
Stout, J. C.
使用可伸缩3D水凝胶产生的HPSC来源的纹状体细胞在亨廷顿病小鼠模型中促进恢复。
影响因子：
5.9
作者：
Adil MM;Gaj T;Rao AT;Kulkarni RU;Fuentes CM;Ramadoss GN;Ekman FK;Miller EW;Schaffer DV
通讯作者：
Schaffer DV