Klopstock Thomas, Videnovic Aleksandar, Bischoff Almut Turid, Bonnet Cecilia, Cif Laura, Comella Cynthia, Correa-Vela Marta, Escolar Maria L, Fraser Jamie L, Gonzalez Victoria, Hermanowicz Neal, Jech Robert, Jinnah Hyder A, Kmiec Tomasz, Lang Anthony, Martí Maria J, Mercimek-Andrews Saadet, Monduy Migvis, Nimmo Graeme A M, Perez-Dueñas Belen, Pfeiffer Helle Cecilie Viekilde, Planellas Lluis, Roze Emmanuel, Thakur Nivedita, Tochen Laura, Vanegas-Arroyave Nora, Zorzi Giovanna, Burns Colleen, Greblikas Feriandas
Friedrich Baur Institute at the Department of Neurology, University Hospital, LMU Munich, Munich, Germany.
German Center for Neurodegenerative Diseases (DZNE), Munich, Munich, Germany.
Mov Disord. 2021 Jun;36(6):1342-1352. doi: 10.1002/mds.28392. Epub 2020 Nov 16.
Pantothenate kinase-associated neurodegeneration (PKAN) currently has no approved treatments.
The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression.
This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL.
Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was -0.09 (-1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups.
Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
泛酸激酶相关神经变性病（PKAN）目前尚无获批的治疗方法。
磷酸泛酰巯基乙胺替代疗法关键试验研究了磷酸泛酰巯基乙胺治疗是否能改善PKAN症状并稳定疾病进展。
这项随机、双盲、安慰剂对照、多中心研究在24周的双盲期内评估了每日口服3次、每次300mg的磷酸泛酰巯基乙胺与安慰剂的疗效。纳入年龄在6至65岁、PANK2基因存在致病变异且PKAN日常生活活动能力（PKAN-ADL）量表评分≥6分的患者。患者按体重和年龄分层，随机接受活性药物（磷酸泛酰巯基乙胺）或安慰剂治疗。主要疗效终点是第24周时PKAN-ADL相对于基线的变化。
在2017年7月23日至2018年12月18日期间，84例患者被随机分组（磷酸泛酰巯基乙胺组：n = 41；安慰剂组：n = 43）；所有84例患者均纳入分析。安慰剂组有6例患者停止治疗；2例肌张力障碍加重，2例依从性差，另有2例分别死于PKAN相关并发症（喂食时误吸和因呼吸衰竭导致的疾病进展）。磷酸泛酰巯基乙胺组和安慰剂组PKAN-ADL的基线平均（标准差）评分分别为28.2（11.4）和27.4（11.5），第24周时分别为26.9（12.5）和24.5（11.8）。第24周时，磷酸泛酰巯基乙胺组与安慰剂组的最小二乘均值差异（95%置信区间）为-0.09（-1.69至1.51；P = 0.9115）。磷酸泛酰巯基乙胺组（8/41；19.5%）和安慰剂组（6/43；14.0%）治疗中出现的严重不良事件总体发生率相似。
磷酸泛酰巯基乙胺治疗是安全的，但并未改善PKAN患者通过PKAN-ADL评估的功能。© 2020作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。
