Trial of Deferiprone in Parkinson's Disease

被引：145

作者：

Devos, David ^{[1
]}

Labreuche, Julien ^{[4
]}

Rascol, Olivier ^{[10
,11
]}

Corvol, Jean-Christophe ^{[12
,13
]}

Duhamel, Alain ^{[4
]}

Delannoy, P. Guyon ^{[5
]}

Poewe, Werner ^{[26
]}

Compta, Yaroslau ^{[27
]}

Pavese, Nicola ^{[31
]}

Ruzicka, Evzen ^{[35
,36
,37
]}

Dusek, Petr ^{[35
,36
,37
]}

Post, Bart ^{[38
]}

Bloem, Bastiaan R. ^{[38
]}

Berg, Daniela ^{[41
]}

Maetzler, Walter ^{[41
]}

Otto, Markus ^{[42
]}

Habert, Marie-Odile ^{[14
,15
,16
]}

Lehericy, Stephane ^{[17
]}

Ferreira, Joaquim ^{[47
]}

Dodel, Richard ^{[43
]}

Tranchant, Christine ^{[19
]}

Eusebio, Alexandre ^{[20
,21
]}

Thobois, Stephane ^{[22
]}

Marques, Ana-Raquel ^{[23
]}

Meissner, Wassilios G. ^{[24
,52
,53
]}

Ory-Magne, Fabienne ^{[10
,11
]}

Walter, Uwe ^{[44
,45
]}

de Bie, Rob M. A. ^{[39
,40
]}

Gago, Miguel ^{[49
,50
]}

Vilas, Dolores ^{[30
]}

Kulisevsky, Jaime ^{[28
,29
]}

Januario, Cristina ^{[51
]}

Coelho, Miguel V. S. ^{[48
]}

Behnke, Stefanie ^{[46
]}

Worth, Paul ^{[32
]}

Seppi, Klaus ^{[26
]}

Ouk, Thavarak ^{[5
,6
]}

Potey, Camille ^{[5
,6
]}

Leclercq, Celine ^{[5
,6
]}

Viard, Romain ^{[2
]}

Kuchcinski, Gregory ^{[2
]}

Lopes, Renaud ^{[2
]}

Pruvo, Jean-Pierre ^{[2
]}

Pigny, Pascal ^{[7
]}

Garcon, Guillaume ^{[8
]}

Simonin, Ophelie ^{[8
]}

Carpentier, Jessica ^{[8
]}

Rolland, Anne-Sophie ^{[1
]}

Nyholm, Dag ^{[54
]}

Scherfler, Christoph

机构：

[1] Univ Lille, Network Ctr Excellence Neurodegenerat CoEN Ctr,De, CHU Lille,Dept Med Pharmacol,Team DVCD,INSERM,UMR, Lille Ctr Excellence Neurodegenerat Disorders LiC, Lille, France

[2] Univ Lille, Network Ctr Excellence Neurodegenerat CoEN Ctr,De, CHU Lille,Dept Neuroradiol,Team DVCD,INSERM,UMRS, Lille Ctr Excellence Neurodegenerat Disorders LiC, Lille, France

[3] Univ Lille, Network Ctr Excellence Neurodegenerat CoEN Ctr,De, CHU Lille,Dept Neurol,Team DVCD,INSERM,UMRS 1172, Lille Ctr Excellence Neurodegenerat Disorders LiC, Lille, France

[4] Univ Lille, CHU Lille, Dept Biostat, Lille, France

[5] CHU Lille, Direct Rech & Innovat, Lille, France

[6] CHU Lille, Vigilance Essais Clin & Serv Pharmacol, Lille, France

[7] CHU Lille, Ctr Biol Pathol, Lab Biochim Hormonol, Lille, France

[8] Univ Lille, CHU Lille, Inst Pasteur Lille, Impact Environm Chim Sante Humaine ULR4483, Lille, France

[9] Univ Lille, CHU Lille, INSERM, Unite Degenerat & Vasc Cognit Disorders 1172, Lille, France

[10] Univ Toulouse 3, Univ Hosp Toulouse, Clin Invest Ctr 1436, Dept Neurosci, Toulouse, France

[11] Univ Toulouse 3, Univ Hosp Toulouse, Dept Clin Pharmacol, NS Park FCRIN Network & NeuroToul CoEN Ctr,INSERM, Toulouse, France

[12] Sorbonne Univ, AP HP, CNRS, INSERM, Paris, France

[13] Hop La Pitie Salpetriere, Ctr Invest Clin Neurosci, Inst Cerveau & Moelle Epiniere ICM, Paris Brain Inst,Dept Neurol, Paris, France

[14] Sorbonne Univ, CNRS, INSERM, Lab Imagerie Biomed, Paris, France

[15] Hop La Pitie Salpetriere, AP HP, Dept Nucl Med, Paris, France

[16] Sorbonne Univ, CEA, Ctr Acquisit & Traitement Images, ICM,CNRS,INSERM,APHP, Paris, France

[17] Sorbonne Univ, Hop Pitie Salpetriere, AP HP,INSERM,Unite 1127,Dept Neuroradiol, Paris Brain Inst ICM,Ctr Neuroimaging Res,CNRS 72, Paris, France

[18] Sorbonne Univ, INSERM, Unite 1127, ICM,CNRS,UMR 7725, Paris, France

[19] Univ Strasbourg, Strasbourg Univ Hosp, Federat Med Translat Strasbourg, Dept Neurol,NS Park FCRIN Network, Strasbourg, France

[20] Timone Univ Hosp, AP HM, Dept Neurol & Movement Disorders, Marseille, France

[21] Aix Marseille Univ, CNRS, Inst Neurosci Timone, UMR 7289, Marseille, France

[22] Univ Lyon, Hosp Civils Lyon, Hop Neurolog Pierre Wertheimer, CNRS,UMR 5229,Serv Neurol,Ctr Expert Parkinson NS, Lyon, France

[23] Univ Clermont Auvergne, Clermont Ferrand Univ Hosp, Dept Neurol, EA7280, Clermont Ferrand, France

[24] Univ Bordeaux, CHU Bordeaux, Serv Neurol Malad Neurodegenerat, Inst Malad Neurodegenerat IMN Clin,CNRS,IMN,UMR 5, Bordeaux, France

[25] Univ Paris Saclay, CEA, CNRS, NeuroSpin,Baobab, Gif Sur Yvette, France

[26] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria

[27] Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer,Parkinsons, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain

[28] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, Movement Disorders Unit,Neurol Dept,Dept Med, Barcelona, Spain

[29] CIBERNED, Barcelona, Spain

[30] Hosp Badalona Germans Trias & Pujol, Movement Disorders Unit, Badalona, Spain

[31] Newcastle Univ, Clin Ageing Res Unit, Newcastle Upon Tyne, Tyne & Wear, England

[32] Addenbrookes Hosp, Cambridge, England

[33] Univ Cambridge, Cambridge Biomed Campus, ALBORADA Drug Discovery Inst, Cambridge, England

[34] Parkinsons UK, London, England

[35] Charles Univ Prague, Dept Neurol, Prague, Czech Republic

[36] Charles Univ Prague, Fac Med 1, Ctr Clin Neurosci, Prague, Czech Republic

[37] Gen Univ Hosp, Prague, Czech Republic

[38] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, Nijmegen, Netherlands

[39] Univ Amsterdam, Dept Neurol, Amsterdam UMC Locat, Amsterdam, Netherlands

[40] Amsterdam Neurosci, Neurodegenerat, Amsterdam, Netherlands

[41] Christian Albrechts Univ Kiel, Dept Neurol, Kiel, Germany

[42] Univ Clin, Dept Neurol, Ulm, Germany

[43] Univ Duisburg Essen, Dept Geriatr Med, Essen, Germany

[44] Rostock Univ, Med Ctr, Dept Neurol, Rostock, Germany

[45] German Ctr Neurodegenerat Dis, Res Site Rostock, Rostock, Germany

[46] Univ Hosp Saarland, Homburg, Germany

[47] Univ Lisbon, Fac Arquitetura, Ctr Invest Arquitetura Urbanismo & Design, Lisbon, Portugal

[48] Hosp Santa Maria, Lisbon, Portugal

[49] Hosp Senhora Oliveira, Dept Neurol, Guimaraes, Portugal

[50] Univ Minho, Sch Med, Life & Hlth Sci Res Inst, Braga, Portugal

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2022年 / 387卷 / 22期

基金：

欧盟地平线“2020”;

关键词：

DOPAMINE TRANSPORTER; IRON CHELATION;

D O I：

10.1056/NEJMoa2209254

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2045 / 2055

页数：11

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