An open label study of a novel immunosuppression intervention for the treatment of amyotrophic lateral sclerosis
An open label study of a novel immunosuppression intervention for the treatment of amyotrophic lateral sclerosis
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DOI：
10.1080/21678421.2017.1421666
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发表时间：
2018-01-01
影响因子：
2.8
通讯作者：
Glass, Jonathan D.
中科院分区：
文献类型：
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作者：
Fournier, Christina N.;Schoenfeld, David;Glass, Jonathan D.
神经炎症越来越多地与肌萎缩侧索硬化症（ALS）的疾病进展有关。在首次人体试验中，脊髓内同种异体干细胞治疗ALS的参与者接受了免疫抑制，其中一名参与者在多个结局指标上都有显着改善。本研究（NCT 01884571）的主要目的是评估ALS患者对巴利昔单抗、他克莫司、霉酚酸酯和泼尼松相同免疫抑制方案的临床应答率。临床反应定义为在6个月内修订的ALS功能评定量表（ALSFRS-R）改善6分。31名参与者入组了这项为期15个月的开放标签研究，并接受了相同的免疫抑制方案。在治疗方案之前、期间和之后收集临床结局指标和生物标本。没有患者符合预定义的应答者标准。与给药前阶段相比，在给药阶段未观察到平均ALSFRS-R斜率的差异（p=0.200）。该方案在ALS人群中通常是安全的，尽管31例患者中只有18例完成了完整的6个月免疫抑制。免疫标志物分析显示，与治疗前相比，治疗期间外周调节性T细胞群无变化（p=0.200）。脑脊液（CSF）细胞因子水平分析显示，免疫抑制后IL-2水平升高（p=0.004），随后在治疗后随访期间降低（p=0.031）。需要进一步的研究来了解免疫系统的操纵如何影响ALS的疾病进展。
Neuroinflammation is increasingly tied to disease progression in amyotrophic lateral sclerosis (ALS). Participants in the first-in-human trial of intra-spinal allogeneic stem cell therapy for ALS received immunosuppression, and one participant saw dramatic improvement across multiple outcome measures. The primary objective of this study (NCT01884571) was to assess the rate of clinical response to the same immunosuppressive regimen using basiliximab, tacrolimus, mycophenolate, and prednisone in people with ALS. A clinical response was defined as an improvement on the revised ALS Functional Rating Scale (ALSFRS-R) by six points over a 6-month period. Thirty-one participants were enrolled in this 15-month open label study and received an identical immunosuppression regimen. Clinical outcome measures and biospecimens were collected before, during, and after the treatment regimen. No patients met the pre-defined responder criteria. No difference in mean ALSFRS-R slope was seen in the treatment period compared to the pretreatment period (p=0.200). The regimen was generally safe in an ALS population, although only 18 out of 31 patients completed the full 6 months of immunosuppression. Analyses of immune markers showed no change in peripheral regulatory T-cell populations during treatment compared to pretreatment (p=0.200). Analysis of cerebrospinal fluid (CSF) cytokine levels showed an increase in IL-2 levels with immunosuppression (p=0.004) followed by decrease during post-treatment follow-up (p=0.031). Further studies are needed to understand how manipulation of the immune system may affect disease progression in ALS.