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

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, U.; Forni, Gian Luca

doi:10.1016/j.parkreldis.2014.03.002

Cited by 81 publications

(60 citation statements)

References 7 publications

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“…Overall major therapeutic outcomes have been generally observed in FA patients treated with L1 during the clinical trials with both neurological and heart function improvements. It should be emphasised that complete clearance of excess cardiac iron in TM and brain iron in neurodegenerative disease patients has been previously achieved using higher doses of L1 over longer periods and the same result is expected in FA patients [112][113][114]119,131] . These optimistic results offer hope to FA patients who otherwise have no other effective treatment.…”

Section: The Role Of Deferiprone In the Treatment Of Friedreich Ataxiamentioning

confidence: 78%

Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases

Kolnagou

Kontoghiorghe

Kontoghiorghes

2014

WJM

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Author contributions: Kolnagou A reviewed the organisational health structure of thalassaemia and Friedreich ataxia in Cyprus; Kontoghiorghe CN contributed the literature background on recent developments on thalassaemia and Friedreich ataxia and critically reviewed the clinical and other aspects of the manuscript; Kontoghiorghes GJ designed, wrote and edited the manuscript including the mechanisms of iron chelation therapy and iron metabolism and toxicity. AbstractThalassaemia major (TM) and Friedreich's ataxia (FA) are autosomal recessive inherited diseases related to the proteins haemoglobin and frataxin respectively. In both diseases abnormalities in iron metabolism is the main cause of iron toxicity leading to increased morbidity and mortality. Major efforts are directed towards the prevention of these diseases and also in their treatment using iron chelation therapy. Both TM and FA are endemic in Cyprus, where the frequency per total population of asymptomatic heterozygote carriers and patients is the highest worldwide. Cyprus has been a pioneering nation in preventing and nearly eliminating the birth of TM and FA patients by introducing an organized health structure, including prenatal and antenatal diagnosis. Effective iron chelation therapy, improved diagnostic methods and transfusion techniques as well as supportive therapy from other clinical specializations have improved the survival and quality of life of TM patients.Despite the tiresome clinical management regimes many TM patients are successful in their professional lives, have families with children and some are now living well into their fifties. The introduction of deferiprone led to the elimination of cardiac failure induced by iron overload toxicity, which was the major cause of mortality in TM. Effective combinations of deferiprone with deferoxamine in TM patients caused the fall of body iron to normal physiological ranges. In FA different mechanisms of iron metabolism and toxicity apply to that of TM, which can be targeted with specific iron chelation protocols. Preliminary findings from the introduction of deferiprone in FA patients have increased the hopes for improved and effective therapy in this untreatable condition. New and personalised treatments are proposed in TM and FA. Overall, advances in treatments and in particular of chelation therapy using deferiprone are transforming TM and FA from fatal to chronic conditions. The paradigm of Cyprus in the prevention and treatment of TM can be used for application worldwide.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Thalassaemia; Friedreich ataxia; Prenatal diagnosis; Survival; Chelation therapy; Deferiprone; Deferoxamine; Cyprus Core tip: Thalassaemia major (TM) and Friedreich's ataxia (FA) are inherited diseases related to iron toxicity, with high morbidity and mortality rates. Cyprus has the highest frequency of TM and FA worldwide. Prenatal diagnosis and other health policies almost abolished the birth of TM and FA patients in Cyprus. Deferiprone has increa...

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Section: The Role Of Deferiprone In the Treatment Of Friedreich Ataxiamentioning

confidence: 78%

Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases

Kolnagou

Kontoghiorghe

Kontoghiorghes

2014

WJM

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“…Typically, the age-at-onset is later compared to other NBIA forms and focal siderosis is observed in the GP. Mild to moderate clinical benefit and stabilization during follow-up lasting 6-48 months was observed in 3 out of 4 documented idiopathic NBIA patients treated with 30 mg/kg/day deferiprone [71,72,84,85].…”

Section: Other Nbia Disordersmentioning

confidence: 91%

“…Successful iron removal from the GP without concomitant clinical improvement may indicate either that irreversible damage has already occurred, or that iron is not the causative agent in PKAN. In another study 30 mg/kg/day deferiprone treatment led to clinical stabilization in four of five PKAN patients, persistent at a 4-year follow-up [71,72]. However, clinical stabilization may be a misleading outcome measure in PKAN patients since the clinical progression in the atypical (late onset) form is nonlinear with rapid deterioration in the first five years and relative stabilization after that [73].…”

Section: Pantothenate Kinase-associated Neurodegenerationmentioning

confidence: 99%

Iron chelation in the treatment of neurodegenerative diseases

Dušek

Schneider

Aaseth

2016

Journal of Trace Elements in Medicine and Biology

101

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a b s t r a c tDisturbance of cerebral iron regulation is almost universal in neurodegenerative disorders. There is a growing body of evidence that increased iron deposits may contribute to degenerative changes. Thus, the effect of iron chelation therapy has been investigated in many neurological disorders including rare genetic syndromes with neurodegeneration with brain iron accumulation as well as common sporadic disorders such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. This review summarizes recent advances in understanding the role of iron in the etiology of neurodegeneration. Outcomes of studies investigating the effect of iron chelation therapy in neurodegenerative disorders are systematically presented in tables. Iron chelators, particularly the blood brain barrier-crossing compound deferiprone, are capable of decreasing cerebral iron in areas with abnormally high concentrations as documented by MRI. Yet, currently, there is no compelling evidence of the clinical effect of iron removal therapy on any neurological disorder. However, several studies indicate that it may prevent or slow down disease progression of several disorders such as aceruloplasminemia, pantothenate kinase-associated neurodegeneration or Parkinson's disease.

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“…Dystonia and spasticity are usually managed with anticholinergic drugs, benzodiazepines, botulinum toxin, oral baclofen and intrathecal baclofen in severe cases. The role of the brain iron accumulation in the pathophysiology of the disease remains under discussion, and iron chelation therapy has been investigated as a disease modifying approach 1,14,17 .…”

Section: Pantothenase Kinase-associated Neurodegeneration (Pkan)mentioning

confidence: 99%

A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging

Salomao

Pedroso

Gama

et al. 2016

Arq. Neuro-Psiquiatr.

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Neurodegeneration with brain iron accumulation (NBIA) represents a heterogeneous and complex group of inherited neurodegenerative diseases, characterized by excessive iron accumulation, particularly in the basal ganglia. Common clinical features of NBIA include movement disorders, particularly parkinsonism and dystonia, cognitive dysfunction, pyramidal signs, and retinal abnormalities. The forms of NBIA described to date include pantothenase kinase-associated neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN), neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein-associated neurodegeneration (MPAN), fatty acid hydroxylase-associated neurodegeneration (FAHN), coenzyme A synthase protein-associated neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome. This review is a diagnostic approach for NBIA cases, from clinical features and brain imaging findings to the genetic etiology.

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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

Cited by 81 publications

References 7 publications

Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases

Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases

Iron chelation in the treatment of neurodegenerative diseases

A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging

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