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

dc.rights.licenseopenen_US
dc.contributor.authorDEVOS, David
dc.contributor.authorRASCOL, Olivier
dc.contributor.authorMEISSNER, Wassilios G
hal.structure.identifierInstitut des Maladies Neurodégénératives [Bordeaux] [IMN]
hal.structure.identifierCentre d'investigation clinique de Toulouse [CIC 1436]
hal.structure.identifierUniversité de Bordeaux [UB]
hal.structure.identifierCentre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
hal.structure.identifierInstitut de Santé Publique, d'Épidémiologie et de Développement (ISPED)
hal.structure.identifierCHU de Bordeaux Pellegrin [Bordeaux]
hal.structure.identifierCIC Bordeaux
hal.structure.identifierBordeaux population health [BPH]
hal.structure.identifierFrench-Clinical Research Infrastructure Network - F-CRIN [Paris] [Cardiovascular & Renal Clinical Trialists - CRCT ]
dc.contributor.authorSAMIER FOUBERT, Alexandra
dc.contributor.authorLEWIS, Simon
dc.contributor.authorTRANCHANT, Christine
dc.contributor.authorANHEIM, Mathieu
dc.contributor.authorMALTETE, David
dc.contributor.authorREMY, Philippe
dc.contributor.authorEGGERT, Karla
dc.contributor.authorPAPE, Heidi
dc.contributor.authorGENY, Christian
dc.contributor.authorCOURATIER, Philippe
dc.contributor.authorCARROLL, Camille
dc.contributor.authorSHERIDAN, Ray
dc.contributor.authorBURN, David
dc.contributor.authorPAVESE, Nicola
dc.contributor.authorRAW, Jason
dc.contributor.authorBERG, Daniela
dc.contributor.authorSUCHOWERSKY, Oksana
dc.contributor.authorKALIA, Lorraine V
dc.contributor.authorEVANS, Andrew
dc.contributor.authorDRAPIER, Sophie
dc.contributor.authorDANAILA, Teodor
dc.contributor.authorSCHNITZLER, Alfons
dc.contributor.authorCORVOL, Jean-Christophe
dc.contributor.authorDEFER, Gilles
dc.contributor.authorTEMIN, Noemi Toiber
dc.contributor.authorFRADETTE, Caroline
dc.contributor.authorTRICTA, Fernando
dc.contributor.authorMOREAU, Caroline
dc.contributor.authorA PARKINSON'S DISEASE STUDY, Group
dc.date.accessioned2025-04-14T11:55:49Z
dc.date.available2025-04-14T11:55:49Z
dc.date.issued2024-12-27
dc.identifier.issn1877-718Xen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/206184
dc.description.abstractEnBACKGROUND: Reducing nigrostriatal iron overload reduces neuronal loss in Parkinson's disease (PD) models. OBJECTIVE: Examine the safety and efficacy of deferiprone in reducing motor disability progression in dopaminergic-treated and treatment-naïve patients with early-stage PD. METHODS: Two 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. RESULTS: Overall, 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. CONCLUSIONS: SKY 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. Parkinson's disease is an age-related brain condition that can lead to problems with movement, muscle cramps, mental health, and pain. People with Parkinson's disease also struggle with activities of daily living that can reduce their well-being. Researchers have found that some people with Parkinson's disease have high levels of iron in their brain. Currently, we do not know if removing iron from the brain can help people with Parkinson's disease. In this study, we examined if a medicine that removes iron from the brain could improve symptoms of Parkinson's disease. This medicine is called deferiprone. Our study included 176 people with Parkinson's disease. People were then divided into 2 groups. In the first group, people were already being treated for Parkinson's disease and then were given deferiprone for 9 months. We found that a low or high dose of deferiprone did not improve disease symptoms. In the second group, people taking no other medication for their Parkinson's disease were given deferiprone for 9 months. In this group, deferiprone worsened Parkinson's symptoms. There are currently no arguments in favor of using deferiprone in Parkinson's disease. Deferiprone without L-dopa worsens symptoms. Research could potentially evaluate low doses of iron chelator in combination with L-dopa over the long term and in large numbers of people. eng
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/*
dc.subject.enParkinson's Disease
dc.subject.enDeferiprone
dc.subject.enDopamine
dc.subject.enIron Chelation
dc.subject.enNeuroprotection
dc.title.enTherapeutic modalities of deferiprone in Parkinson's disease: SKY and EMBARK studies
dc.title.alternativeJ Parkinsons Disen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1177/1877718x241300295en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed39973479en_US
bordeaux.journalJournal of Parkinson's diseaseen_US
bordeaux.page72-86en_US
bordeaux.volume15en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamACTIVE_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Journal%20of%20Parkinson's%20disease&amp;rft.date=2024-12-27&amp;rft.volume=15&amp;rft.issue=1&amp;rft.spage=72-86&amp;rft.epage=72-86&amp;rft.eissn=1877-718X&amp;rft.issn=1877-718X&amp;rft.au=DEVOS,%20David&amp;RASCOL,%20Olivier&amp;MEISSNER,%20Wassilios%20G&amp;SAMIER%20FOUBERT,%20Alexandra&amp;LEWIS,%20Simon&amp;rft.genre=article


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