Therapeutic modalities of deferiprone in Parkinson's disease: SKY and EMBARK studies.

IF 4 3区 医学 Q2 NEUROSCIENCES
Journal of Parkinson's disease Pub Date : 2025-02-01 Epub Date: 2024-12-27 DOI:10.1177/1877718X241300295
David Devos, Olivier Rascol, Wassilios G Meissner, Alexandra Foubert-Samier, Simon Lewis, Christine Tranchant, Mathieu Anheim, David Maltête, Philippe Remy, Karla Eggert, Heidi Pape, Christian Geny, Philippe Couratier, Camille Carroll, Ray Sheridan, David Burn, Nicola Pavese, Jason Raw, Daniela Berg, Oksana Suchowersky, Lorraine V Kalia, Andrew Evans, Sophie Drapier, Teodor Danaila, Alfons Schnitzler, Jean-Christophe Corvol, Gilles Defer, Noemi Toiber Temin, Caroline Fradette, Fernando Tricta, Caroline Moreau
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引用次数: 0

Abstract

BackgroundReducing nigrostriatal iron overload reduces neuronal loss in Parkinson's disease (PD) models.ObjectiveExamine the safety and efficacy of deferiprone in reducing motor disability progression in dopaminergic-treated and treatment-naïve patients with early-stage PD.MethodsTwo phase II, multicenter studies, SKY and EMBARK, enrolled patients diagnosed with early PD (<3 years from screening). In SKY, patients on stable dopaminergic therapy were randomized 1:1 to one of four dosage (or placebo-matching) cohorts (300, 600, 900, 1200 mg twice daily [BID]) for 9 months. EMBARK enrolled patients on stable dopaminergic therapy or treatment-naïve patients and received 15 mg/kg BID. For both studies, the primary outcome was the change from baseline to month 9 in motor examination score (Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] Part III). ClinicalTrials.gov: NCT02728843; ANZCTR: ACTRN12617001578392.ResultsOverall, 140 patients were randomized in SKY (28 per cohort). Thirty-six patients enrolled in EMBARK (27 dopaminergic-treated; 9 treatment-naïve). In the SKY study, all doses showed the same worsening as the placebo group, with the exception of the 600 mg dose, which was associated with non-significant reductions in MDS-UPDRS Part III least-squares mean (LSM) between baseline and 9 months (-2-8 points versus placebo). In EMBARK, LSM (SE) changes from baseline in MDS-UPDRS Part III were nonsignificant (-1.6 [1.7]) and significant (8.3 [3.9]) for dopaminergic-treated and treatment-naïve patients, respectively, the latter indicating disease worsening. Adverse events possibly related to deferiprone were reported in 35.7%-88.9% across all deferiprone groups vs. 42.9% for placebo.ConclusionsSKY and EMBARK studies indicate that deferiprone combined with L-dopa does not provide significant motor function benefit, while the absence of L-dopa treatment worsens symptoms.

去铁素在帕金森病中的治疗方式:SKY和EMBARK研究。
背景:减少黑质纹状体铁超载可减少帕金森病(PD)模型中的神经元损失。目的:探讨去铁素在多巴胺能治疗和treatment-naïve早期PD患者中减少运动障碍进展的安全性和有效性。方法:两项II期多中心研究SKY和EMBARK纳入了诊断为早期PD的患者(结果:总体而言,140例患者在SKY中随机分配(每个队列28例)。36例患者入组EMBARK(27例接受多巴胺能治疗;9首次治疗)。在SKY研究中,除600 mg剂量外,所有剂量均显示出与安慰剂组相同的恶化情况,该剂量与基线至9个月期间MDS-UPDRS第三部分最小二乘平均值(LSM)的无显著降低相关(与安慰剂相比-2-8点)。在EMBARK中,多巴胺能治疗和treatment-naïve患者的LSM (SE)较基线变化不显著(-1.6[1.7]),显著(8.3[3.9]),后者表明疾病恶化。可能与去铁酮相关的不良事件在所有去铁酮组中报告的发生率为35.7%-88.9%,而安慰剂组为42.9%。结论:SKY和EMBARK研究表明,去铁酮联合左旋多巴不能显著改善运动功能,而不使用左旋多巴会加重症状。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.40
自引率
5.80%
发文量
338
审稿时长
>12 weeks
期刊介绍: The Journal of Parkinson''s Disease (JPD) publishes original research in basic science, translational research and clinical medicine in Parkinson’s disease in cooperation with the Journal of Alzheimer''s Disease. It features a first class Editorial Board and provides rigorous peer review and rapid online publication.
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