Title :

Ceruloplasmin activity and iron chelation treatment of patients with parkinson's disease

Author(s) :

Grolez, Guillaume [Auteur]
moreau, caroline [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U1171
Lille Neurosciences & Cognition (LilNCog) - U 1172
Sablonniere, Bernard [Auteur]

Lille Neurosciences & Cognition (LilNCog) - U 1172
Garcon, Guillaume [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Devedjian, Jean-Christophe [Auteur]
Meguig, Sayah [Auteur]
Gele, Patrick [Auteur]
Delmaire, Christine [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Troubles cognitifs dégénératifs et vasculaires - U1171
Bordet, Regis [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Troubles cognitifs dégénératifs et vasculaires - U1171
DEFEBVRE, Luc [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Troubles cognitifs dégénératifs et vasculaires - U1171
Cabantchik, Ioav Zvi [Auteur]
DEVOS, DAVID [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Troubles cognitifs dégénératifs et vasculaires - U1171

Journal title :

BMC neurology

Abbreviated title :

BMC Neurol.

Volume number :

15

Publication date :

2015-05-06

ISSN :

1471-2377

English keyword(s) :

Motor response
L-dopa
Deferiprone
Parkinson''s disease
Iron chelation

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

BACKGROUND: Growing body of evidence suggests that Parkinson's disease (PD) is associated with oxidative damage via iron accumulation in the substantia nigra (SN). Low ceruloplasmin (CP)-ferroxidase activity has been ...
Show more >BACKGROUND: Growing body of evidence suggests that Parkinson's disease (PD) is associated with oxidative damage via iron accumulation in the substantia nigra (SN). Low ceruloplasmin (CP)-ferroxidase activity has been identified in the SN and the cerebrospinal fluid (CSF) of patients with PD. The iron chelator, deferiprone, reduces the abnormally high levels of iron in the SN. In order to determine CP's involvement in iron accumulation in SN and PD progression, we aim to compare the ability of iron chelation treatment to reducing both SN iron levels and motor handicap in PD patients according to the level of ceruloplasmin activity. METHODS: We used a moderate chelation protocol with deferiprone (DFP) based on a, 6-month delayed-start paradigm, randomized placebo controlled clinical trial in 40 PD patients. CP-ferroxidase activity was determined in blood and CSF together with the D544E gene polymorphism (rs701753). Iron levels were determined by R2* MRI sequence and the motor handicap by the UPDRS motor score. RESULTS: After 6 to 12 months of DFP treatment, greater reductions in SN iron levels and UPDRS motor scores were obtained in patients with higher serum and CSF levels of CP-ferroxidase activity. After 6 months of DFP treatment, the AT genotype group displayed greater reduction of iron level in the SN with greater CSF and serum levels of CP activity than the AA genotype group. CONCLUSIONS: Although most of the DFP-treated patients displayed clinical and radiological improvements, those with the lower CP activity appeared to respond better to iron chelation. Larger RCTs are now needed to establish whether pharmacological modulation of CP activity could be an innovative neuroprotective strategy in PD. BACKGROUND: FAIR-PARK study (ClinicalTrials.gov reference: NCT00943748 ; French national reference number: 2008-006842-25). This study was approved by the French Drug Agency (ANSM) and the local institutional review board ("Comité de Protection des Personnes of Lille").Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
CNRS
Inserm
Institut Pasteur de Lille
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Research team(s) :

Troubles cognitifs dégénératifs et vasculaires

Submission date :

2019-11-27T13:37:14Z
2020-02-19T10:28:14Z
2022-10-19T13:49:40Z
2022-10-21T15:55:03Z