Efficacy and Safety of the Iron Chelator Deferiprone in Parkinson's Disease
Status:
Completed
Trial end date:
2011-10-01
Target enrollment:
Participant gender:
Summary
Few available drugs can slow the progression of neurodegenerative pathologies such as
Parkinson's disease (PD). One of the recent hypotheses concerning the reduction of oxidative
stress and neuron death features a harmful effect of iron, which may reach abnormally high
levels in the substantia nigra (SN) pars compacta (iron overload has been seen in the
substantia nigra in parkinsonian patients and in the
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD). Iron overload is
harmful because it reacts with hydrogen peroxide (H2O2) produced during the oxidative
deamination of dopamine, generating hydroxyl radicals which then damage proteins, DNA and
phospholipid membranes and may be responsible for neuron death. The use of an iron chelator
(clioquinol) produces a reduction in neuron death in the MPTP mouse model. In humans, a
special, partially refocused interleaved multiple echo (PRIME) MR sequence has been used to
study the relaxation time (T2*) and quantify iron overload in the SN of PD patients and the
nucleus dentatus of patients with Friedreich's ataxia. T2* sequences have revealed a decrease
in iron overload following treatment with the chelator deferiprone, in parallel with a
clinical improvement in these patients. Furthermore, the very recent open label use of
deferiprone in rare serious, systemic, neurological iron overload diseases (Neurodegeneration
with Brain Iron Accumulation (NBIA)) has revealed a clinical improvement after 6 months, with
2 case reports from our group and another from an Italian group (Forni et al., 2008). The
safety of the low dosages of deferiprone (20 to 30 mg/kg/day) used in neurology appears to be
much greater than for the high dosages (75 to 100 mg/kg/day in 3 doses) used in hematology to
decrease post-transfusion iron overloads in thalassemia major.
Hence, the investigators wish to evaluate the effect of treatment with an oral iron chelator
which is capable of crossing the blood-brain barrier (deferiprone) on iron overload in the
SN(as assessed by the T2* sequence) with respect to the progression of clinical sign in PD.
It is expected a 6-month course of deferiprone able to produce a moderate reduction in iron
overload of the SN, associated with a drop in the motor handicap score. Depending on the
risk/benefit balance determined in this initial pilot study, a larger, multicenter
neuroprotection study could be envisaged.