Objective: To investigate whether treatment with the iron-chelating drug deferiprone (DFP) has benefit in patients with pantothenate kinase-associated neurodegeneration (PKAN), the most common form of neurodegeneration with brain iron accumulation (NBIA).

Background: PKAN is a rare genetic disorder characterized by progressive dystonia and iron accumulation in the globus pallidus. Reduction of brain iron might slow the progression of symptoms. The iron chelator DFP can cross the blood-brain barrier and remove labile iron from neuronal cells.

Methods: Eighty-nine PKAN patients were randomized in a 2:1 ratio to receive either DFP or matching placebo for 18 months. Efficacy was assessed using the Barry-Albright Dystonia (BAD) scale, the Patient Global Impression of Improvement (PGI-I), and numerous tests of functional abilities and activities of daily living. Brain iron was measured at baseline and month 18 using MRI R2*.

Results: After 18 months, MRI showed a sharp drop in brain iron in the DFP group while the placebo group had virtually no change, for a treatment group difference of -35.6 Hz (p < 0.0001). In a predefined subgroup analysis that looked separately at patients with classic vs. atypical PKAN, deferiprone use was associated with a significantly (p=0.0187) slower progression of the disease (2.19 points less) than placebo in patients with atypical PKAN. In patients with classic PKAN, the group difference of 0.81 points in favour of deferiprone did not reach significance (p=0.5701). For all patients combined, deferiprone-treated patients worsened by 1.51 points less than the placebo group (p=0.0761). No significant differences were seen on other efficacy measures, but there was a pattern suggesting an effect for deferiprone on the majority of measures. With regard to safety, deferiprone was well tolerated.

Conclusions: Patients with PKAN who received DFP for 18 months showed a significant decrease in brain iron and a non-significant trend suggesting slower progression of symptoms as compared to patients who received placebo. Note: Similar abstracts on the results of this study have been submitted for the congress of the European Academy of Neurology, June 16-19, 2018 (accepted) and for the congress of the American Academy of Neurology, April 21-27, 2018 (acceptance pending)

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-randomized-trial-of-deferiprone-for-pantothenate-kinase-associated-neurodegeneration/