Objective: To assess the safety of iron chelation in the treatment of regional brain iron overload.

Background: Excess brain iron is evident in neurodegenerative diseases such as Parkinson’s disease (PD), Friedreich ataxia, and Neurodegeneration with Brain Iron Accumulation (NBIA), and thus, a potential target for therapy. However, use of iron chelation has been limited, partly due to concerns around systemic iron depletion. Deferiprone (DFP) is an iron chelator that crosses the blood-brain barrier, removes excess intracellular iron, and excretes or redistributes it to biologic receptors for metabolic reutilization. These properties decrease the risk of iron depletion, making DFP a suitable candidate for regional iron chelation. Three studies exploring DFP in PD are ongoing and two in NBIA are completed, providing valuable data on its safety in such patients.

Method: Patients with pantothenate kinase-associated neurodegeneration, the most common form of NBIA, were randomized 2:1 to receive DFP or placebo for 18 months. Study completers could enroll in an extension study where all received DFP for 18 additional months. Efficacy results are provided elsewhere.

Results: In the randomized study (N=58 for DFP, 30 for placebo), rates of adverse events were similar between the groups, except for freezing phenomenon (0% for DFP vs. 10%, for placebo p=0.0370) and anemia (21% for DFP, 0% for placebo, p=0.0067) although only 3 patients with anemia had hemoglobin <10 g/d. Non-significant differences were seen in rates of decreased serum ferritin (33% vs. 17%; p=0.1341) and iron deficiency (16% vs. 10%; p=0.7442). Iron supplements were taken by 39% of DFP and 27% of placebo patients. There were no events of agranulocytosis and no significant difference in the rates of less severe neutropenia (9% vs. 7%). In the extension study (N=68), DFP continued to be well tolerated. There were two deaths, both unrelated to the drug. The most common adverse events were dystonia (59% of patients), fever (34%), headache (29%), condition aggravated (27%) and decreased serum ferritin (27%).

Conclusion: DFP therapy for up to 36 months in patients with excess brain iron was well tolerated and was not associated with any unexpected safety concerns. Events related to iron reduction were modest and did not raise a clinical concern. These data provide evidence in support of the safety of DFP for the reduction of brain iron accumulation and its investigation in patients with PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/safety-of-iron-chelation-in-patients-with-brain-iron-overload/