ProjektFAIR-PARK-II – Conservative iron chelation as a disease-modifying strategy in Parkinson's disease: a multicentric,…
Grunddaten
Akronym:
FAIR-PARK-II
Titel:
Conservative iron chelation as a disease-modifying strategy in Parkinson's disease: a multicentric, parallel-group, placebo-controlled, randomized clinical trial of deferiprone
Laufzeit:
01.05.2015 bis 30.04.2020
Abstract / Kurz- beschreibung:
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.
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.
Schlüsselwörter:
Disease modifier
Iron chelation
Oxidative stress
Neuroprotektion
neuroprotection
klinische Studie
clinical trial
Parkinsonerkrankung
Parkinson's disease
Beteiligte Mitarbeiter/innen
Leiter/innen
Berg, Daniela
Neurologische Universitätsklinik
Kliniken und klinische Institute, Medizinische Fakultät
Kliniken und klinische Institute, Medizinische Fakultät
Neurologische Universitätsklinik
Kliniken und klinische Institute, Medizinische Fakultät
Kliniken und klinische Institute, Medizinische Fakultät
Lokale Einrichtungen
Abteilung Neurologie mit Schwerpunkt Neurodegenerative Erkrankungen
Neurologische Universitätsklinik
Kliniken und klinische Institute, Medizinische Fakultät
Kliniken und klinische Institute, Medizinische Fakultät
Geldgeber
Brüssel, Belgien
Brüssel, Belgien