Iron chelation in the treatment of neurodegenerative diseases

Abstract

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.

Infratentorial superficial siderosis: Classification, diagnostic criteria, and rational investigation pathway

“…37 However, agranulocytosis is a potentially serious side effect of deferiprone. 38 Observational reports suggest that defining and treating causal structural anomalies (eg, surgical repair or blood patches to seal dural defects 17 might be of benefit, but large-scale controlled studies are lacking. An observational trial of deferiprone in superficial siderosis (ClinicalTrials.gov identifier: NCT01284127), with a planned follow-up period of 2 years, has completed recruitment but is not yet published.…”

Aceruloplasminemia: A Severe Neurodegenerative Disorder Deserving an Early Diagnosis

“…However, the overall efficacy of iron chelation therapy in neurodegenerative disorders with brain iron accumulation is difficult to assess because of the lack of standardized description of clinical and MRI findings in ACP patients. According to a recent review, “there is no compelling evidence of the clinical effect of iron removal therapy on any neurological disorder,” including ACP (Dusek et al, 2016). Moreover poor tolerance to iron chelators, even including worsening of anemia due to further iron subtraction for erythropoiesis, has been often reported, limiting the long-term use of such agents that would be required to mobilize iron from the brain (Miyajima and Hosoi, 1993–2018; Mariani et al, 2004; Pelucchi et al, 2018).…”

Medical treatment of dystonia

“…Treatment with miglustat (N-butyl-deoxynojirimycin) has been shown to improve or stabilize neurological manifestations [35, 36]. Neurodegeneration with brain iron accumulation (NBIA), another example of heavy metal-related disorders, has been reported to benefit from iron chelation with deferiprone [37, 38], although this needs further study.Even when an etiology-specific approach is available, symptomatic medical therapies can still be employed as an adjunct or bridging therapy until the specific treatment achieves maximal benefit. For example, in Wilson’s disease, anticholinergics can be used to symptomatically treat dystonia concurrently with copper chelation.…”

“…Treatment with miglustat (N-butyl-deoxynojirimycin) has been shown to improve or stabilize neurological manifestations [35, 36]. Neurodegeneration with brain iron accumulation (NBIA), another example of heavy metal-related disorders, has been reported to benefit from iron chelation with deferiprone [37, 38], although this needs further study.…”