Weiterer Beitrag zur Kenntnis der Hallervorden-Spatzschen Krankheit

Gallyas, Ferenc; Környey, St.

doi:10.1007/bf00341968

Cited by 10 publications

(2 citation statements)

References 9 publications

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“…Deferoxamine, which does not cross the intact BBB, did not have value for PKAN when it was administered for 6 months at 250 mg/day by intramuscular injection (Gallyas and Környey, 1968). However, deferiprone, which does cross the BBB, did lessen brain iron but did not improve clinical symptoms in a study of nine patients with PKAN (12.5 mg of deferiprone/kg, twice daily for 6 months) (Zorzi et al, 2011).…”

Section: Iron Chelation Therapy Has Yielded Mixed Results For Non-demmentioning

confidence: 99%

Iron Chelation and Multiple Sclerosis

2013

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Histochemical and MRI studies have demonstrated that MS (multiple sclerosis) patients have abnormal deposition of iron in both gray and white matter structures. Data is emerging indicating that this iron could partake in pathogenesis by various mechanisms, e.g., promoting the production of reactive oxygen species and enhancing the production of proinflammatory cytokines. Iron chelation therapy could be a viable strategy to block iron-related pathological events or it can confer cellular protection by stabilizing hypoxia inducible factor 1α, a transcription factor that normally responds to hypoxic conditions. Iron chelation has been shown to protect against disease progression and/or limit iron accumulation in some neurological disorders or their experimental models. Data from studies that administered a chelator to animals with experimental autoimmune encephalomyelitis, a model of MS, support the rationale for examining this treatment approach in MS. Preliminary clinical studies have been performed in MS patients using deferoxamine. Although some side effects were observed, the large majority of patients were able to tolerate the arduous administration regimen, i.e., 6–8 h of subcutaneous infusion, and all side effects resolved upon discontinuation of treatment. Importantly, these preliminary studies did not identify a disqualifying event for this experimental approach. More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood–brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen.

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Section: Iron Chelation Therapy Has Yielded Mixed Results For Non-demmentioning

confidence: 99%

Iron Chelation and Multiple Sclerosis

2013

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“…The first report was published in 1968 when Gallyas and Kornyey used desferrioxamine for the treatment of an NBIA disorder not further molecularly characterized (as prior to the genetic era) (15). There was no clinical improvement.…”

Section: Iron Chelation Iron Chelation For Pkanmentioning

confidence: 99%

Emerging Disease-Modifying Therapies in Neurodegeneration With Brain Iron Accumulation (NBIA) Disorders

et al. 2021

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Neurodegeneration with Brain Iron Accumulation (NBIA) is a heterogeneous group of progressive neurodegenerative diseases characterized by iron deposition in the globus pallidus and the substantia nigra. As of today, 15 distinct monogenetic disease entities have been identified. The four most common forms are pantothenate kinase-associated neurodegeneration (PKAN), phospholipase A2 group VI (PLA2G6)-associated neurodegeneration (PLAN), beta-propeller protein-associated neurodegeneration (BPAN) and mitochondrial membrane protein-associated neurodegeneration (MPAN). Neurodegeneration with Brain Iron Accumulation disorders present with a wide spectrum of clinical symptoms such as movement disorder signs (dystonia, parkinsonism, chorea), pyramidal involvement (e.g., spasticity), speech disorders, cognitive decline, psychomotor retardation, and ocular abnormalities. Treatment remains largely symptomatic but new drugs are in the pipeline. In this review, we discuss the rationale of new compounds, summarize results from clinical trials, provide an overview of important results in cell lines and animal models and discuss the future development of disease-modifying therapies for NBIA disorders. A general mechanistic approach for treatment of NBIA disorders is with iron chelators which bind and remove iron. Few studies investigated the effect of deferiprone in PKAN, including a recent placebo-controlled double-blind multicenter trial, demonstrating radiological improvement with reduction of iron load in the basal ganglia and a trend to slowing of disease progression. Disease-modifying strategies address the specific metabolic pathways of the affected enzyme. Such tailor-made approaches include provision of an alternative substrate (e.g., fosmetpantotenate or 4′-phosphopantetheine for PKAN) in order to bypass the defective enzyme. A recent randomized controlled trial of fosmetpantotenate, however, did not show any significant benefit of the drug as compared to placebo, leading to early termination of the trials' extension phase. 4′-phosphopantetheine showed promising results in animal models and a clinical study in patients is currently underway. Another approach is the activation of other enzyme isoforms using small molecules (e.g., PZ-2891 in PKAN). There are also compounds which counteract downstream cellular effects. For example, deuterated polyunsaturated fatty acids (D-PUFA) may reduce mitochondrial lipid peroxidation in PLAN. In infantile neuroaxonal dystrophy (a subtype of PLAN), desipramine may be repurposed as it blocks ceramide accumulation. Gene replacement therapy is still in a preclinical stage.

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Hallervorden-Spatz Syndrome

Dooling¹,

Schoene²,

Richardson³

1974

Archives of Neurology

244

125

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(Fig 1) (Fig 3). Lewy bodies were also found within neurons of the substantia innominata and of the locus ceruleus.The cerebral cortex in general showed no cytoarchitectural abnormalities or changes in the nerve fibers or glia (except for the expected scarring at the biopsy site). Adja¬ cent to many of the nerve cells, espe¬ cially in the frontal and insular cortex, there were hyaline eosinophilic bodies of rounded or irregular contour, which in their appearance and staining properties resembled the swollen axons seen else¬ where; but they differed from the Lewy bodies (Fig 4). These structures, identified as juxtaneuronal axonal swellings, could also be found in the cerebral biopsy speci¬ men. In the hippocampus, many of the pyramidal neurons showed granulovacuolar degeneration.

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Weiterer Beitrag zur Kenntnis der Hallervorden-Spatzschen Krankheit

Cited by 10 publications

References 9 publications

Iron Chelation and Multiple Sclerosis

Iron Chelation and Multiple Sclerosis

Emerging Disease-Modifying Therapies in Neurodegeneration With Brain Iron Accumulation (NBIA) Disorders

Hallervorden-Spatz Syndrome

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