法国里尔大学医院中心David Devos团队研究了去铁酮延缓早期帕金森病的疗效。这一研究成果发表在2022年11月30日出版的《新英格兰医学杂志》上。

帕金森症患者黑质中的铁含量增加，或有助于该疾病的病理生理学。早期研究表明，铁螯合剂去铁酮可以降低帕金森病患者黑质纹状体铁含量，但其对疾病进展的影响尚不清楚。

研究组进行了一项多中心、临床2期、随机、双盲试验，参与者为新确诊的帕金森病患者，从未服用左旋多巴。将参与者按1:1的比例随机分配接受口服去铁酮，剂量为每公斤体重15毫克，每天两次，或服用安慰剂，持续36周。除非认为有必要控制症状，否则禁止使用多巴胺能治疗。

主要结局是36周时，运动障碍协会赞助的统一帕金森氏病评定量表（MDS-UPDRS；范围为0至260，评分越高表示受损越严重）总评分发生的变化。40周内的次要和探索性临床结局包括运动和非运动残疾的测量。使用磁共振成像测量大脑铁含量也是一个探索性结果。

共有372名参与者入选；186名被分配接受去铁酮，186名接受安慰剂。症状进展导致去铁酮组22.0%的参与者和安慰剂组2.7%的参与者开始多巴胺能治疗。基线时，去铁酮组MDS-UPDRS平均总分为34.3分，安慰剂组为33.2分，36周时分别增加（恶化）15.6分和6.3分，组间差异显著。与安慰剂组相比，去铁酮组的黑质铁含量下降更多。去铁酮的主要严重不良事件是2名参与者的粒细胞缺乏症和3名参与者的中性粒细胞减少症。

研究结果表明，在从未接受过左旋多巴治疗且未计划使用多巴胺能药物治疗的早期帕金森病患者中，在36周的时间内，与安慰剂组相比，去铁酮与帕金森病评分更差相关。

附：英文原文

Title: Trial of Deferiprone in Parkinson’s Disease

Author: David Devos, M.D., Ph.D.,, Julien Labreuche, Ph.D.,, Olivier Rascol, M.D., Ph.D.,, Jean-Christophe Corvol, M.D., Ph.D.,, Alain Duhamel, M.D., Ph.D.,, Pauline Guyon Delannoy, M.L.S.,, Werner Poewe, M.D., Ph.D.,, Yaroslau Compta, M.D., Ph.D.,, Nicola Pavese, M.D., Ph.D.,, Even Rika, M.D., Ph.D.,, Petr Duek, M.D., Ph.D.,, Bart Post, M.D., Ph.D.,, Bastiaan R. Bloem, M.D., Ph.D.,, Daniela Berg, M.D.,, Walter Maetzler, M.D.,, Markus Otto, M.D., Ph.D.,, Marie-Odile Habert, Ph.D.,, Stéphane Lehericy, M.D., Ph.D.,, Joaquim Ferreira, M.D., Ph.D.,, Richard Dodel, M.D.,, Christine Tranchant, M.D., Ph.D.,, Alexandre Eusebio, M.D., Ph.D.,, Stéphane Thobois, M.D., Ph.D.,, Ana-Raquel Marques, M.D., Ph.D.,, Wassilios G. Meissner, M.D., Ph.D.,, Fabienne Ory-Magne, M.D., Ph.D.,, Uwe Walter, M.D., Ph.D.,, Rob M.A. de Bie, M.D., Ph.D.,, Miguel Gago, M.D., Ph.D.,, Dolores Vilas, M.D., Ph.D.,, Jaime Kulisevsky, M.D., Ph.D.,, Cristina Januario, M.D., Ph.D.,, Miguel V.S. Coelho, M.D., Ph.D.,, Stefanie Behnke, M.D., Ph.D.,, Paul Worth, M.D., Ph.D.,, Klaus Seppi, M.D., Ph.D.,, Thavarak Ouk, Pharm.D., Ph.D.,, Camille Potey, Pharm.D., Ph.D.,, Céline Leclercq, M.S.,, Romain Viard, Ph.D.,, Gregory Kuchcinski, M.D., Ph.D.,, Renaud Lopes, Ph.D.,, Jean-Pierre Pruvo, M.D., Ph.D.,, Pascal Pigny, Pharm.D., Ph.D.,, Guillaume Garon, Ph.D.,, Ophélie Simonin, M.S.,, Jessica Carpentier, M.S.,, Anne-Sophie Rolland, Ph.D.,, Dag Nyholm, M.D., Ph.D.,, Christoph Scherfler, M.D., Ph.D.,, Jean-Franois Mangin, Ph.D.,, Marie Chupin, Ph.D.,, Régis Bordet, M.D., Ph.D.,, David T. Dexter, M.D., Ph.D.,, Caroline Fradette, M.D., Ph.D.,, Michael Spino, Pharm.D.,, Fernando Tricta, M.D.,, Scott Ayton, Ph.D.,, Ashley I. Bush, M.D., Ph.D.,, Jean-Christophe Devedjian, Ph.D.,, James A. Duce, Ph.D.,, Ioav Cabantchik, M.D., Ph.D.,, Luc Defebvre, M.D., Ph.D.,, Dominique Deplanque, M.D., Ph.D.,, and Caroline Moreau, M.D., Ph.D.

Issue&Volume: 2022-11-30

Abstract:

Background

Iron content is increased in the substantia nigra of persons with Parkinson’s disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson’s disease, but its effects on disease progression are unclear.

Methods

We conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson’s disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome.

Results

A total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants.

Conclusions

In participants with early Parkinson’s disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks.

DOI: 10.1056/NEJMoa2209254

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2209254