Efficacy and safety of deferiprone for the treatment of pantothenate kinase-associated neurodegeneration (PKAN) and neurodegeneration with brain iron accumulation (NBIA): Results from a four years follow-up

• Published in: Parkinsonism & related disorders 2014-06, Vol.20 (6), p.651-654
• Main Authors: Cossu, Giovanni, Abbruzzese, Giovanni, Matta, Gildo, Murgia, Daniela, Melis, Maurizio, Ricchi, Valeria, Galanello, Renzo, Barella, Susanna, Origa, Raffaella, Balocco, Manuela, Pelosin, Elisa, Marchese, Roberta, Ruffinengo, Uberto, Forni, Gian Luca
• Format: Article
• Language: English
• Subjects: Adult; Deferiprone; Female; Humans; Iron; Iron Chelating Agents - therapeutic use; Iron Metabolism Disorders - diagnosis; Iron Metabolism Disorders - drug therapy; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; NBIA; Neuroaxonal Dystrophies - diagnosis; Neuroaxonal Dystrophies - drug therapy; Neurology; Pantothenate Kinase-Associated Neurodegeneration - diagnosis; Pantothenate Kinase-Associated Neurodegeneration - drug therapy; PKAN; Pyridones - therapeutic use; Severity of Illness Index; Young Adult
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2014.03.002

Abstract Objective To evaluate the long-term effect of Deferiprone (DFP) in reducing brain iron overload and improving neurological manifestations in patients with NBIA. Methods 6 NBIA patients (5 with genetically confirmed PKAN), received DFP solution at 15 mg/kg po bid. They were assessed by UPDRS/III and UDRS scales and blinded video rating, performed at baseline and every six months. All patients underwent brain MRI at baseline and during follow up. Quantitative assessment of brain iron was performed with T2* relaxometry, using a gradient multi-echo T2* sequence. Results After 48 months of treatment clinical rating scales and blinded video rating indicated a stabilization in motor symptoms in 5/6 Pts. In the same subjects MRI evaluation showed reduced hypointensity in the globus pallidus (GP); quantitative assessment confirmed a significant increment in the T2* value, and hence reduction of the iron content of the GP. Conclusion The data from our 4-years follow-up study confirm the safety of DFP as a chelator agent for iron accumulation. The clinical stabilization observed in 5/6 of our patients suggests that DFP may be a reasonable therapeutic option for the treatment of the neurological manifestations linked with iron accumulation and neurodegeneration, especially in adult patients at early stage of the disease. (Clinicaltrials.gov identifier: NTC00907283).