Safety and efficacy of intensive task-specific training in people with recent spinal cord injury: a phase 3, pragmatic, randomised, assessor-blinded, superiority trial

近期脊髓损伤患者强化特定任务训练的安全性和有效性：一项 3 期、实用性、随机、评估者设盲的优效性试验

It is widely believed that intensive task-specific training enhances neurological recovery in people with spinal cord injury (SCI) by exploiting activity-dependent spinal plasticity. We aimed to determine whether 10 weeks of intensive task-specific training supplemented with strength training that targets motor function at and below the level of the lesion improves recovery following recent SCI. Intensive task-specific training supplemented with strength training provided in people with recent SCI did not result in significant benefits on our primary and secondary clinical outcomes. The evidence does not support any beneficial effect of additional training for those receiving usual inpatient rehabilitation care from a multi-disciplinary team.

人们普遍认为，强化的特定任务训练通过利用依赖活动的脊髓可塑性，可促进脊髓损伤（SCI）患者的神经功能恢复。我们旨在确定，针对损伤平面及以下运动功能的 10 周强化特定任务训练并辅以力量训练，是否能改善近期发生脊髓损伤后的恢复情况。对近期脊髓损伤患者进行强化特定任务训练并辅以力量训练，并未使我们的主要和次要临床结局获得显著改善。现有证据不支持多学科团队提供的常规住院康复护理之外的额外训练具有有益效果。

REF: Glinsky JV, Chu J, Rimmer C, et al. Safety and efficacy of intensive task-specific training in people with recent spinal cord injury: a phase 3, pragmatic, randomised, assessor-blinded, superiority trial. Lancet Neurol. 2026;25(3):234-244. doi:10.1016/S1474-4422(26)00010-4 PMID: 41722590

Safety and efficacy of fordadistrogene movaparvovec in ambulatory participants with Duchenne muscular dystrophy (CIFFREO): a phase 3, double-blind, randomised, placebo-controlled study

福达迪司妥基因莫帕帕沃韦在可独立行走的杜氏肌营养不良症患者中的安全性和有效性（CIFFREO）：一项3期、双盲、随机、安慰剂对照研究

Gene transfer is a promising therapeutic approach for Duchenne muscular dystrophy as the disease results from mutations in a single gene. Fordadistrogene movaparvovec is an investigational recombinant adeno-associated virus 9 (rAAV9)-based vector encoding a mini-dystrophin transgene protein for Duchenne muscular dystrophy . We aimed to assess the safety and efficacy of fordadistrogene movaparvovec in slowing the functional decline experienced by individuals with Duchenne muscular dystrophy. The study did not meet its primary efficacy endpoint. Based on the efficacy and safety data from this phase 3 study, the benefit-risk profile of fordadistrogene movaparvovec was determined to be negative. Thus, the study sponsor has discontinued any further clinical development of this investigational gene therapy agent.

由于杜氏肌营养不良症是由单个基因突变所致，基因转移是一种很有前景的治疗方法。福达迪司托基因莫帕帕韦克是一种处于研究阶段的基于重组腺相关病毒9（rAAV9）的载体，其编码用于治疗杜氏肌营养不良症的微型抗肌萎缩蛋白转基因。我们旨在评估福达迪司托基因莫帕帕韦克在减缓杜氏肌营养不良症患者功能衰退方面的安全性和有效性。该研究未达到其主要疗效终点。根据这项3期研究的疗效和安全性数据，福达迪司托基因莫帕帕韦克的获益 - 风险比被判定为负面。因此，研究发起者已停止对这种处于研究阶段的基因治疗药物进行进一步的临床开发。

REF: Muntoni F, Nascimento A, Shin J, et al. Safety and efficacy of fordadistrogene movaparvovec in ambulatory participants with Duchenne muscular dystrophy (CIFFREO): a phase 3, double-blind, randomised, placebo-controlled study. Lancet Neurol. 2026;25(3):245-255. doi:10.1016/S1474-4422(26)00036-0 PMID: 41722591

Safety and efficacy of eslicarbazepine acetate for seizure prevention in patients with stroke at high risk of developing post-stroke epilepsy: a proof-of-concept, phase 2a, randomised, double-blind, placebo-controlled antiepileptogenesis trial

醋酸艾司利卡西平预防有较高卒中后癫痫发生风险的卒中患者癫痫发作的安全性和有效性：一项概念验证性 2a 期随机双盲安慰剂对照抗癫痫发生试验

Eslicarbazepine acetate is an antiseizure medication that has shown potential antiepileptogenic effects in preclinical models of epilepsy. We aimed to investigate whether eslicarbazepine acetate could prevent or reduce the incidence of unprovoked seizures after acute ischaemic stroke or acute intracerebral haemorrhage. The proportion of patients who had a first unprovoked seizure, died, or discontinued at 6 months did not differ significantly between the eslicarbazepine acetate and placebo groups. However, the trial was underpowered owing to slow recruitment and the COVID-19 pandemic, producing wide confidence intervals. The findings indicate that antiepileptogenesis studies are feasible, and guide the design of adequately powered trials with clinically meaningful endpoints.

醋酸艾司利卡西平是一种抗癫痫药物，在癫痫临床前模型中显示出潜在的抗癫痫发生作用。我们旨在研究醋酸艾司利卡西平能否预防或降低急性缺血性中风或急性脑出血后无诱因癫痫发作的发生率。在6个月时，首次出现无诱因癫痫发作、死亡或停药的患者比例在醋酸艾司利卡西平组和安慰剂组之间无显著差异。然而，由于招募速度缓慢和新冠疫情的影响，该试验的检验效能不足，导致置信区间较宽。这些研究结果表明抗癫痫发生研究是可行的，并为设计具有足够检验效能且有临床意义终点的试验提供了指导。

REF: Koepp MJ, Trinka E, Mah YH, et al. Safety and efficacy of eslicarbazepine acetate for seizure prevention in patients with stroke at high risk of developing post-stroke epilepsy: a proof-of-concept, phase 2a, randomised, double-blind, placebo-controlled antiepileptogenesis trial. Lancet Neurol. 2026;25(3):256-267. doi:10.1016/S1474-4422(25)00491-0 PMID: 41722592

A path to preventing cognitive impairment due to Alzheimer's disease: initiatives beginning in the USA

预防阿尔茨海默病所致认知障碍的途径：始于美国的举措

Antibody therapies can remove amyloid plaques from the brain and slow cognitive decline in people with Alzheimer's disease who are mildly impaired. These drugs are now being evaluated in participants who are cognitively unimpaired but positive for a biomarker of Alzheimer's disease for their safety, tolerability, disease-modifying and cognitive preserving effects, and ability to avert the onset of cognitive impairment. If these studies are successful, and the drugs get regulatory approval, they could accelerate the evaluation and approval of related Alzheimer's disease-modifying treatments in people who are unimpaired with or without a biomarker of the disease. Preclinical Alzheimer's disease therapies that modify the underlying disease in people who are unimpaired with a biomarker of Alzheimer's disease and primary prevention therapies that avert the onset of amyloid plaques in those with a negative test have the potential to substantially prevent ensuing biological and clinical manifestations of Alzheimer's disease. In this Policy View, we assess the challenges and opportunities that trials of these drug treatments will bring, and consider the blood tests, cognitive assessments, and post-marketing strategies needed to enable the approval, affordability, health-care insurance coverage, and equitable use. Our recommendations are intended for consideration in the USA, and relevant refinement in other countries.

抗体疗法可以清除大脑中的淀粉样蛋白斑块，并减缓轻度受损的阿尔茨海默病患者的认知衰退。目前正在认知功能未受损但阿尔茨海默病生物标志物呈阳性的参与者中评估这些药物的安全性、耐受性、疾病修饰和认知保护作用，以及预防认知障碍发作的能力。如果这些研究取得成功，且药物获得监管部门批准，它们可能会加速对认知功能未受损、无论是否有该病生物标志物的人群进行相关阿尔茨海默病修饰疗法的评估和审批。针对有阿尔茨海默病生物标志物但认知功能未受损人群的临床前阿尔茨海默病疗法（可改变潜在疾病状况），以及针对生物标志物检测呈阴性人群的一级预防疗法（可预防淀粉样蛋白斑块出现），有可能大幅预防阿尔茨海默病随后出现的生物学和临床症状。在这篇政策观点文章中，我们评估了这些药物治疗试验将带来的挑战和机遇，并考虑了为实现药物获批、可负担性、医疗保险覆盖和公平使用所需的血液检测、认知评估和上市后策略。我们的建议供美国参考，其他国家可进行相关调整。

REF: Reiman EM, Alexander RC, Langbaum JB, et al. A path to preventing cognitive impairment due to Alzheimer's disease: initiatives beginning in the USA. Lancet Neurol. 2026;25(3):268-278. doi:10.1016/S1474-4422(25)00483-1 PMID: 41722593

Advances in migraine prevention

偏头痛预防的进展

Migraine imposes a heavy burden on patients and societies. Preventive treatments aimed at reducing the occurrence of migraine attacks and their intensity have been largely underused, leaving a multitude of people with migraine to rely exclusively on acute treatments, which, when used in excess, might even worsen the clinical situation. Large, randomised trials have established the tolerability and efficacy of calcitonin gene-related peptide (CGRP)-targeting drugs, a new class of migraine-specific treatment. The increased adherence to longer treatment cycles with migraine-specific preventive drugs, such as CGRP-targeting therapies, compared with non-migraine specific treatments has the potential to improve control of the disease. These migraine-specific drugs also provide benefits to individuals with migraine who previously did not benefit from non-specific migraine preventive medications. Increased reliance on preventive treatment with migraine-specific options is progressively optimising the management of migraine for mounting numbers of patients disabled by the disease, thereby improving disease control and their quality of life.

偏头痛给患者和社会带来了沉重负担。旨在减少偏头痛发作次数和减轻发作强度的预防性治疗在很大程度上未得到充分利用，导致众多偏头痛患者只能完全依赖急性治疗，而过度使用急性治疗甚至可能使临床情况恶化。大型随机试验已证实了降钙素基因相关肽（CGRP）靶向药物（一类新型偏头痛特异性治疗药物）的耐受性和有效性。与非偏头痛特异性治疗相比，偏头痛特异性预防药物（如CGRP靶向疗法）在更长治疗周期中的依从性提高，有可能改善疾病控制情况。这些偏头痛特异性药物还能让那些之前使用非特异性偏头痛预防药物无效的偏头痛患者受益。越来越多地依赖偏头痛特异性预防治疗方案，正逐步优化大量因该病而失能患者的偏头痛管理，从而改善疾病控制状况并提高他们的生活质量。

REF: Martinelli D, De Icco R, Al-Khazali HM, et al. Advances in migraine prevention. Lancet Neurol. 2026;25(3):279-293. doi:10.1016/S1474-4422(25)00477-6 PMID: 41722594