Intraspinal stem cell transplantation for amyotrophic lateral sclerosis.
Intraspinal stem cell transplantation for amyotrophic lateral sclerosis.
复制标题
DOI：
10.1002/ana.24584
复制
发表时间：
2016-03
影响因子：
11.2
通讯作者：
Feldman EL
中科院分区：
文献类型：
--
作者：
Chen KS;Sakowski SA;Feldman EL
肌萎缩性侧索硬化症（ALS）是一种毁灭性的神经退行性疾病，上肢和下肢运动神经元的丧失会导致进行性无力并最终死亡。利鲁唑是FDA批准的唯一一种中度减缓ALS进展的药物，自批准以来的几十年里，没有出现新的治疗方法来改变疾病的进程。这部分是由于我们对运动神经元退化的复杂发病机制的理解不完全。干细胞已经成为治疗ALS的一个有吸引力的选择，因为它们具有同样复杂的细胞机制，并且可以通过多种方式调节局部微环境来拯救患病的运动神经元。虽然各种干细胞类型正在临床前和早期临床应用中进行评估，但在这里，我们回顾了支持神经祖细胞治疗ALS的临床转化的临床前策略和进展。具体来说，我们专注于脊髓神经祖细胞的使用，以及从临床前研究到涉及人类直接椎管内移植的I期和ii期临床试验设计的管道。
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder in which the loss of upper and lower motor neurons produces progressive weakness and eventually death. In the decades since the approval of riluzole, the only FDA approved medication to moderately slow progression of ALS, no new therapeutics have arisen to alter the course of the disease. This is partly due to our incomplete understanding of the complex pathogenesis of motor neuron degeneration. Stem cells have emerged as an attractive option in treating ALS since they come armed with equally complex cellular machinery and may modulate the local microenvironment in many ways to rescue diseased motor neurons. While various stem cell types are being evaluated in preclinical and early clinical applications, here we review the preclinical strategies and advances supporting the recent clinical translation of neural progenitor cell therapy for ALS. Specifically, we focus on the use of spinal cord neural progenitor cells and the pipeline starting from preclinical studies to the designs of the Phase I and IIa clinical trials involving direct intraspinal transplantation in humans.