Therapeutic modalities of deferiprone in Parkinson's disease: SKY and EMBARK studies - Hospices Civils de Lyon
Article Dans Une Revue Journal of Parkinson's disease Année : 2024

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

Simon Lewis
Philippe Couratier
Camille Carroll
Ray Sheridan
David Burn
Nicola Pavese
Jason Raw
  • Fonction : Auteur
Daniela Berg
Oksana Suchowersky
Andrew Evans
Teodor Danaila
Noemi Toiber Temin
  • Fonction : Auteur
Caroline Fradette
  • Fonction : Auteur correspondant
Fernando Tricta
Caroline Moreau

Résumé

Background 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. 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.
Fichier principal
Vignette du fichier
devos-et-al-2024-therapeutic-modalities-of-deferiprone-in-parkinson-s-disease-sky-and-embark-studies.pdf (1.86 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04867806 , version 1 (06-01-2025)

Licence

Identifiants

Citer

David Devos, Olivier J. Rascol, Wassilios Meissner, Alexandra Foubert-Samier, Simon Lewis, et al.. Therapeutic modalities of deferiprone in Parkinson's disease: SKY and EMBARK studies. Journal of Parkinson's disease, 2024, ⟨10.1177/1877718x241300295⟩. ⟨hal-04867806⟩
0 Consultations
0 Téléchargements

Altmetric

Partager

More