Département d'études cognitives, école normale supérieure, PSL University, 75005 Paris, France; Inserm U955, Institut Mondor de Recherche Biomédicale, Equipe E01 NeuroPsychologie Interventionnelle, 94000 Créteil, France; Faculté de médecine, Université Paris-Est Créteil, 94000 Créteil, France; Assistance Publique-Hôpitaux de Paris, National Reference Center for Huntington's Disease, Neurology Department, Henri Mondor-Albert Chenevier Hospital, Créteil, France.
Rev Neurol (Paris). 2022 May;178(5):441-449. doi: 10.1016/j.neurol.2022.03.004. Epub 2022 Apr 28.
Huntington's disease is a rare, severe, and inherited neurodegenerative disorder that affects young adults. To date, there is no treatment to stop its progression. The primary atrophy of the striatum in HD, is limited in space and centrally focalised in the brain and thus constitutes a good candidate for graft. Therefore, transplantation of foetal cells from the ganglionic eminence, the germinal zone of the striatum, has the potential to restore disrupted fronto-cortical circuits and corresponding clinical functions. The international Multicentric intracerebral Grafting in Huntington's disease trial was not as successful as two pilot trials (Créteil and London) which showed promising results in the 2000s, displaying stabilisation/recovery of symptoms in some patients. A point-by-point comparison of the differences between MIG-HD and the pilot trial from Créteil in which similar data are available provides lessons on the grafting procedure and allows for strategic thinking before embarking on future trials. MIG-HD demonstrated the existence of intracerebral alloimmunisation leading to acute or chronic graft rejection into the brain and showed the limitations of surgical standardisation and immunosuppression. It has also improved the safety of the procedure and provided guidance for the follow-up of future patients. Indeed, even if disease modifiers treatments are currently the focus of intense research, they may not stop or slow the progression of the disease sufficiently, or even be administered in all patients, to prevent brain atrophy in all cases. Although disease-modifying therapies are currently the subject of intense research, they may not stop or slow disease progression sufficiently, or may not be given to all patients to prevent brain atrophy. A combination with intracerebral transplantation to repair the damaged structures may thus prove beneficial. Altogether, pursuing research in intracerebral transplantation remains necessary.
亨廷顿病是一种罕见的、严重的遗传性神经退行性疾病，影响年轻人。迄今为止，尚无治疗方法可以阻止其进展。HD 中纹状体的主要萎缩在空间上是有限的，并且在大脑中集中在中央，因此是移植的良好候选物。因此，移植来自神经节隆起（纹状体的生发区）的胎儿细胞有可能恢复中断的额皮质回路和相应的临床功能。国际多中心脑内移植治疗亨廷顿病试验不如两项试点试验（克雷泰伊和伦敦）成功，这两项试验在 21 世纪显示出了有希望的结果，显示出一些患者的症状稳定/恢复。对 MIG-HD 与具有相似数据的克雷泰伊试点试验之间差异的逐点比较提供了有关移植程序的经验教训，并允许在进行未来试验之前进行战略思考。MIG-HD 证明了存在脑内同种异体免疫，导致大脑内急性或慢性移植物排斥，并显示了手术标准化和免疫抑制的局限性。它还提高了手术的安全性，并为未来患者的随访提供了指导。事实上，即使疾病修饰治疗目前是研究的重点，它们也可能不足以阻止或减缓疾病的进展，甚至可能无法在所有患者中使用，以防止所有情况下的脑萎缩。尽管疾病修饰疗法目前是研究的重点，但它们可能不足以阻止或减缓疾病的进展，或者可能无法在所有患者中使用以防止脑萎缩。因此，与脑内移植相结合以修复受损结构可能会证明是有益的。总之，继续进行脑内移植研究仍然是必要的。
