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Conservative iron chelation as a disease-modifying strategy in Parkinson’s disease: a multicentric, parallel-group, placebo-controlled, randomized clinical trial of deferiprone

Project description

Parkinson’s disease modifying strategy using iron chelation

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. It is associated with iron excess in the substantia nigra, exposing dopaminergic neurons to high levels of oxidative stress resulting from mitochondrial and dopamine metabolism disorders. Previous preclinical and pilot clinical studies demonstrated the effectiveness of a novel iron chelation therapy with deferiprone (DFP) in inducing neuroprotection in PD cell models, as well as slowing the disease progression in mouse models and early-stage PD patients. The objective of the EU-funded FAIR-PARK-II project is to conduct a parallel-group, randomised, placebo-controlled, clinical trial to demonstrate that DFP can slow the progression of disability in de novo PD patients, thereby establishing iron chelation as a disease-modifying treatment in neurodegeneration.

Objective

Parkinson’s disease (PD) is a major, chronic, non-communicable disease and the 2nd most frequent neurodegenerative disorder worldwide. Excess iron is primarily detected in the substantia nigra pars compacta, where dopaminergic neurons are exposed to high levels of oxidative stress produced by mitochondrial disorders and dopamine metabolism. Our previous preclinical, translational and pilot clinical studies demonstrated that novel iron chelation therapy with the prototypic drug deferiprone (DFP) (i) induces neuroprotection in cell models of PD via a powerful antioxidant effect, (ii) reduces regional siderosis of the brain, (iii) reduces motor handicap via inhibition of catechol-o-methyl transferase, and (iv) slows the progression of motor handicap in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model and in early PD patients. This project now seeks to demonstrate that conservative iron chelation therapy with moderate-dose DFP (30 mg/kg/day) slows the progression of handicap in de novo PD patients while not affecting systemic parameters. The 9-month, parallel-group, randomized, placebo-controlled, multicentre trial will be followed by a 1-month wash-out period. The primary efficacy criterion will be the change in motor and non-motor handicap scores on the Total Movement Disorders Society Unified Parkinson’s Disease Rating Scale to identify disease-modifying and symptomatic effects. The secondary efficacy criterion will be the change in score between baseline and 40 weeks (i.e. probing the disease-modifying effect only). Potential surrogate radiological and biological biomarkers, health economics and societal impacts will be assessed. 17 national, European and international research and innovation activities will be linked with the project. The study results should prompt academic and industrial research on iron chelation as a disease-modifying treatment in neurodegenerative diseases.

Call for proposal

H2020-PHC-2014-2015

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Sub call

H2020-PHC-2014-two-stage

Coordinator

CENTRE HOSPITALIER REGIONAL ET UNIVERSITAIRE DE LILLE
Net EU contribution
€ 2 604 799,55
Address
Avenue oscar lambret 2
59037 Lille
France

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Region
Hauts-de-France Nord-Pas de Calais Nord
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 2 604 799,55

Participants (20)