Assistance Publique-Hôpitaux de Paris, National Reference Center for Huntington's Disease, Neurology Department, Henri Mondor-Albert Chenevier Hospital, Créteil, France.
Equipe neuropsychologie interventionnelle, Département d'études cognitives, École normale supérieure, PSL, Research University, Institut Mondor de Recherche biomédicale, Université Paris-Est, INSERM, Paris, and Créteil, France.
Mov Disord. 2020 Aug;35(8):1323-1335. doi: 10.1002/mds.28201. Epub 2020 Jul 15.
Huntington's disease is a rare, severe, inherited neurodegenerative disease in which we assessed the safety and efficacy of grafting human fetal ganglionic eminence intrastriatally.
Patients at the early stage of the disease were enrolled in the Multicentric Intracerebral Grafting in Huntington's Disease trial, a delayed-start phase II randomized study. After a run-in period of 12 months, patients were randomized at month 12 to either the treatment group (transplanted at month 13-month 14) or the control group and secondarily treated 20 months later (month 33-month 34). The primary outcome was total motor score compared between both groups 20 months postrandomization (month 32). Secondary outcomes included clinical, imaging, and electrophysiological findings and a comparison of pregraft and postgraft total motor score slopes during the entire study period (month 0-month 52) regardless of the time of transplant.
Of 54 randomized patients, 45 were transplanted; 26 immediately (treatment) and 19 delayed (control). Mean total motor score at month 32 did not differ between groups (treated controls difference in means adjusted for M12: +2.9 [95% confidence interval, -2.8 to 8.6]; P = 0.31). Its rate of decline after transplantation was similar to that before transplantation. A total of 27 severe adverse events were recorded in the randomized patients, 10 of which were related to the transplant procedure. Improvement of procedures during the trial significantly decreased the frequency of surgical events.We found antihuman leucocytes antigen antibodies in 40% of the patients.
No clinical benefit was found in this trial. This may have been related to graft rejection. Ectopia and high track number negatively influence the graft outcome. Procedural adjustments substantially improved surgical safety. (ClinicalTrials.gov NCT00190450.) © 2020 International Parkinson and Movement Disorder Society.
亨廷顿病是一种罕见的、严重的、遗传性神经退行性疾病，我们评估了将人胎神经节隆起移植到纹状体内部的安全性和有效性。
在疾病早期，患者被纳入多中心脑内移植治疗亨廷顿病试验，这是一项延迟启动的 II 期随机研究。经过 12 个月的导入期后，患者在第 12 个月随机分为治疗组（在第 13 个月至第 14 个月进行移植）或对照组，并在 20 个月后（第 33 个月至第 34 个月）进行二次治疗。主要终点是在随机分组后 20 个月（第 32 个月）两组之间的总运动评分比较。次要终点包括临床、影像学和电生理发现，以及在整个研究期间（第 0 个月至第 52 个月），无论移植时间如何，比较移植前和移植后的总运动评分斜率。
在 54 名随机患者中，45 名接受了移植；26 名立即（治疗），19 名延迟（对照）。第 32 个月时，两组的总运动评分无差异（治疗对照组调整 M12 后均值差异：+2.9[95%置信区间，-2.8 至 8.6]；P=0.31）。移植后其下降速度与移植前相似。在随机患者中记录了 27 例严重不良事件，其中 10 例与移植程序有关。试验过程中程序的改进显著降低了手术事件的频率。我们发现 40%的患者存在抗人类白细胞抗原抗体。
本试验未发现临床获益。这可能与移植物排斥有关。异位和高轨道数对移植物结局有负面影响。程序调整大大提高了手术安全性。（ClinicalTrials.gov NCT00190450。）
