MSAUTO 2002 HEMATOPOIETIC STEM CELL THERAPY FOR PATIENTS WITH MS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。多发性硬化症(MS)最初是一种免疫介导的脱髓鞘疾病。在大多数情况下，它始于一种复发缓解的疾病，发作明显，两次发作之间没有任何症状。在几年或几十年的时间里，几乎所有的病例都会转变为一种进行性疾病，在这种疾病中，无论有没有急性发作，都会出现潜伏的和缓慢的神经恶化。复发-缓解性疾病通常对免疫抑制或调节治疗有反应，而基于免疫的治疗对进展性临床病程的患者通常无效。这种临床病程和对免疫抑制的反应，以及神经病理学和神经成像研究表明，疾病的进展与轴突萎缩有关。与免疫介导的脱髓鞘相比，残疾与轴突萎缩程度的相关性更好。因此，基于免疫的治疗，为了有效，需要在病程早期开始，而MS主要是一种免疫介导性和炎症性疾病。虽然目前基于免疫的疗法延缓了残疾，但尚未证明干预措施可以防止进行性残疾。我们建议，作为II期研究，完全免疫消融，然后在免疫消融前从患者身上采集自体体内淋巴细胞耗尽的干细胞移植进行重建。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Multiple sclerosis (MS) is at onset an immune-mediated demyelinating disease. In most cases, it starts as a relapsing-remitting disease with distinct attacks and no symptoms between flares. Over years or decades, virtually all cases transition into a progressive disease in which insidious and slow neurologic deterioration occurs with or without acute flares. Relapsing-remitting disease is often responsive to immune suppressive or modulating therapies, while immune based therapies are generally ineffective in patients with a progressive clinical course. This clinical course and response to immune suppression, as well as neuropathology and neuroimaging studies, suggest that disease progression is associated with axonal atrophy. Disability correlates better with measures of axonal atrophy than immune mediated demyelination. Therefore, immune based therapies, in order to be effective, need to be started early in the disease course while MS is predominately an immune-mediated and inflammatory disease. While current immune based therapies delay disability, no intervention has been proven to prevent progressive disability. We propose, as a phase II study, complete immune ablation and subsequent reconstitution with autologous in vivo lymphocyte depleted stem cell grafts harvested from the patient prior to immune ablation.