Centre de Recherche du CHUL (CHUQ), Axe Neurosciences, RC-9800, 2705, Boulevard Laurier, Québec, QC, G1V 4G2, Canada.
Brain. 2011 Mar;134(Pt 3):641-52. doi: 10.1093/brain/awq328. Epub 2011 Jan 28.
Cell therapy offers the possibility of replacing degenerated neurons thereby improving the symptoms of neurodegenerative disorders such as Huntington's disease. However, clinical benefits in patients with Huntington's disease, if any, have been transient and modest. Grafts survived well at 18 months in one patient with Huntington's disease, but graft survival was markedly attenuated by 10 years in three other patients from this transplantation cohort. It is critical to delineate the causes of graft degeneration if such therapies will be utilized in patients with a goal of achieving meaningful clinical benefit. Similar challenges may also accrue to future stem cell therapies. Here we discuss the potential causes of suboptimal long-term graft survival in patients with Huntington's disease, including allograft immunoreactivity, microglial responses targeted to grafted cells and cell-to-cell neurotoxicity. We also discuss similar challenges and unique differences comparing neuronal grafts in patients with Parkinson's and Huntington's diseases.
细胞疗法提供了替换退化神经元的可能性，从而改善亨廷顿病等神经退行性疾病的症状。然而，亨廷顿病患者的临床获益如果有的话也是短暂和适度的。在一名亨廷顿病患者中，移植后 18 个月移植物存活良好，但在来自该移植队列的另外 3 名患者中，10 年后移植物存活明显减弱。如果这些疗法将用于亨廷顿病患者以实现有意义的临床获益，那么明确移植物退化的原因至关重要。类似的挑战也可能会出现在未来的干细胞治疗中。在这里，我们讨论了导致亨廷顿病患者长期移植物存活不理想的潜在原因，包括同种异体移植物免疫反应、针对移植细胞的小胶质细胞反应和细胞间神经毒性。我们还讨论了在帕金森病和亨廷顿病患者中神经元移植的类似挑战和独特差异。
