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Lookup NU author(s): Professor Camille CarrollORCiD, Professor David BurnORCiD, Professor Nicola PaveseORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
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.PLAIN LANGUAGE SUMMARY: 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.
Author(s): Devos D, Rascol O, Meissner WG, Foubert-Samier A, Lewis S, Tranchant C, Anheim M, Maltete D, Remy P, Eggert K, Pape H, Geny C, Couratier P, Carroll C, Sheridan R, Burn D, Pavese N, Raw J, Berg D, Suchowersky O, Kalia LV, Evans A, Drapier S, Danaila T, Schnitzler A, Corvol J-C, Defer G, Temin NT, Fradette C, Tricta F, Moreau C
Publication type: Article
Publication status: Published
Journal: Journal of Parkinson's Disease
Year: 2025
Volume: 15
Issue: 1
Pages: 72-86
Print publication date: 01/02/2025
Online publication date: 27/12/2024
Acceptance date: 28/10/2024
Date deposited: 25/04/2025
ISSN (print): 1877-7171
ISSN (electronic): 1877-718X
Publisher: Sage Publications Ltd.
URL: https://doi.org/10.1177/1877718X241300295
DOI: 10.1177/1877718X241300295
Data Access Statement: All data requests should be submitted to the corresponding author for consideration. Chiesi will approve or deny data requests from external parties on a case-by-case basis. Chiesi reserves the right to deny requests for any and all legally appropriate reasons. Data requests that risk sharing participant-level data or proprietary information will not be approved.
PubMed id: 39973479
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