Genetic disorders of
iron metabolism and chronic
inflammation often evoke local
iron accumulation. In
Friedreich ataxia, decreased
iron-sulphur cluster and
heme formation leads to mitochondrial
iron accumulation and ensuing oxidative damage that primarily affects sensory neurons, the myocardium, and endocrine glands. We assessed the possibility of reducing brain
iron accumulation in
Friedreich ataxia patients with a membrane-permeant
chelator capable of shuttling chelated
iron from cells to
transferrin, using regimens suitable for patients with no systemic
iron overload. Brain magnetic resonance imaging (MRI) of
Friedreich ataxia patients compared with age-matched controls revealed smaller and irregularly shaped dentate nuclei with significantly (P < .027) higher H-relaxation rates R2*, indicating regional
iron accumulation. A 6-month treatment with 20 to 30 mg/kg/d
deferiprone of 9 adolescent patients with no overt
cardiomyopathy reduced R2* from 18.3 s(-1) (+/- 1.6 s(-1)) to 15.7 s(-1) (+/- 0.7 s(-1); P < .002), specifically in dentate nuclei and proportionally to the initial R2* (r = 0.90).
Chelator treatment caused no apparent hematologic or neurologic side effects while reducing neuropathy and ataxic gait in the youngest patients. To our knowledge, this is the first clinical demonstration of chelation removing labile
iron accumulated in a specific brain area implicated in a
neurodegenerative disease. The use of moderate chelation for relocating
iron from areas of deposition to areas of deprivation has clinical implications for various neurodegenerative and hematologic disorders.