Clinical Experience With Deferiprone Treatment for Friedreich Ataxia

Abstract

Friedreich ataxia is an inherited disorder characterized by degeneration of the peripheral and central nervous system and hypertrophic cardiomyopathy. Homozygous mutations in the frataxine (FXN) gene reduce expression of frataxin and cause accumulation of iron in the mitochondria. Deferiprone, an oral iron chelator, has been shown effective in cell and animal models of Friedreich ataxia. The results of a 6-month randomized, double blind placebo-controlled study suggested that deferiprone 20 mg/kg/day may reduce disease progression. The authors present their experience of 5 Friedreich ataxia patients treated with deferiprone (20 mg/kg/day), in addition to idebenone treatment, followed over a period of 10-24 months, under off-label authorization. The patients were monitored for laboratory parameters, cardiac assessment, neurological evaluations, and quality of life. The authors conclude that combined therapy of a low dose of deferiprone with idebenone is relatively safe, might improve neurological function, and seems to improve heart hypertrophy, warranting further studies.

Drug Repurposing in Parkinson’s Disease

“…Nevertheless, whether excessive iron represents a cause or consequence of dopaminergic neuronal cell death is uncertain however the short-term efficacy results are highly encouraging. While it remains to be seen whether observed clinical benefits in PD patients occurred as a result of iron chelation alone or via permissive effects of chelation on dopaminergic treatments, other preliminary successes of iron chelation in neurodegenerative disease such as Friedreich's Ataxia [102] provide further support to its potential and further phase II/III trials are now underway. A randomised, double-blind, placebocontrolled trial is underway involving 338 patients with treatment naïve PD patients evaluating the use of deferiprone 30mg/kg/day on the total MDS-UPDRS score at 36 weeks (FAIRPARK-II, NCT02655315); and a randomised, double blind trial of deferiprone in 140 patients with PD assessing doses of deferiprone of 600 to 2400mg/day on the MDS-UPDRS Part 3 over 9 months (SKY, NCT02728843).…”

Quantitative proteomics identifies STEAP4 as a critical regulator of mitochondrial dysfunction linking inflammation and colon cancer

“…To understand if mitochondrial iron dysregulation is a pathophysiologically relevant mechanism, deferiprone (DFP) was assessed. DFP is a clinically approved reagent that can chelate mitochondrial iron (18)(19)(20)(21). DFP effectively protected the body weight loss, preserved colon length, and reduced histological changes and pathological score in DSS-treated STEAP4 transgenic mice (Fig.…”

Keeping heart homeostasis in check through the balance of iron metabolism

“…It is possible that during initial stages, MIO is the primary feature of FA, while in later stages irreversible mitochondrial damage is accompanied by cytosolic iron overload in cardiomyocytes, which could be aggravated by prevention of iron export from molecules such as hepcidin produced by inflammatory cells . Based on these results, low‐dose iron chelator deferiprone has been used to treat cardiac damage in FA in different clinical trials . Other iron chelators are not useful, even have deleterious effects, because of the cellular iron disbalance caused by their higher affinity for iron .…”