Copper-histidine therapy for Menkes disease

Sarkar, Bibudhendra; Lingertat-Walsh, Karen; Clarke, Joe T.R.

doi:10.1016/s0022-3476(05)80870-4

Cited by 121 publications

(81 citation statements)

References 7 publications

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“…To correct systemic copper deficiencies in MD, subcutaneous copper-histidine injection is the standard treatment (10)(11)(12), but its efficacy depends on the age-related maturation of the blood-brain barrier (BBB) or residual copper transport by a partially functional gene (12)(13)(14). When copper treatment is initiated in the neonatal period or early infancy, when the BBB is immature, the injected copper is delivered to the neurons and, thus, is an effective treatment for neurologic disorders (11,14).…”

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confidence: 99%

“…When copper treatment is initiated in the neonatal period or early infancy, when the BBB is immature, the injected copper is delivered to the neurons and, thus, is an effective treatment for neurologic disorders (11,14). However, parenteral copper administration has limited clinical efficacy in MD patients more than 2 mo old because the injected copper is trapped in the maturing BBB (11).…”

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confidence: 99%

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PET Imaging Analysis with ⁶⁴Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model

Nomura

Nozaki²,

Hamazaki

et al. 2014

J Nucl Med

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Menkes disease (MD), an X-linked recessive disorder of copper metabolism caused by mutations in the copper-transporting ATP7A gene, results in growth failure and severe neurodegeneration in early childhood. Subcutaneous copper-histidine injection is the standard treatment for MD, but it has limited clinical efficacy. Furthermore, long-term copper injection causes excess copper accumulation in the kidneys, resulting in renal dysfunction. To attempt to resolve this issue, we used PET imaging with 64 Cu to investigate the effects of disulfiram on copper biodistribution in living mice serving as an animal model for MD (MD model mice). Methods: Macular mice were used as MD model mice, and C3H/He mice were used as wild-type mice. Mice were pretreated with 2 types of chelators (disulfiram, a lipophilic chelator, and D-penicillamine, a hydrophilic chelator) 30 min before 64 CuCl 2 injection. After 64 CuCl 2 injection, emission scans covering the whole body were performed for 4 h. After the PET scans, the brain and kidneys were analyzed for radioactivity with γ counting and autoradiography. Results: After copper injection alone, marked accumulation of radioactivity ( 64 Cu) in the liver was demonstrated in wild-type mice, whereas in MD model mice, copper was preferentially accumulated in the kidneys (25.56 ± 3.01 percentage injected dose per gram [%ID/g]) and was detected to a lesser extent in the liver (13.83 ± 0.26 %ID/g) and brain (0.96 ± 0.08 %ID/g). Copper injection with disulfiram reduced excess copper accumulation in the kidneys (14.54 ± 2.68 %ID/g) and increased copper transport into the liver (29.42 ± 0.98 %ID/g) and brain (5.12 ± 0.95 %ID/g) of MD model mice. Copper injection with D-penicillamine enhanced urinary copper excretion and reduced copper accumulation in most organs in both mouse groups. Autoradiography demonstrated that disulfiram pretreatment induced copper transport into the brain parenchyma and reduced copper accumulation in the renal medulla. Conclusion: PET studies with 64 Cu revealed that disulfiram had significant effects on the copper biodistribution of MD. Disulfiram increased copper transport into the brain and reduced copper uptake in the kidneys of MD model mice. The application of 64 Cu PET for the treatment of MD and other copperrelated disorders may be useful in clinical settings.

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confidence: 99%

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confidence: 99%

PET Imaging Analysis with ⁶⁴Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model

Nomura

Nozaki²,

Hamazaki

et al. 2014

J Nucl Med

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“…Histidine was shown to enhance the uptake of copper in human trophoblast cells in the presence of serum, and this is considered to be due to the release of copper bound to albumin [Mas and Sarkar, 1992]. These findings led us to use copper-histidine in the treatment of Menkes disease [Sarkar, 1980[Sarkar, , 1984Procopis et al, 1981;Danks, 1988;Nadal and Baerlocher, 1988;Sherwood et al, 1989;Sarkar et al, 1993]. Subcutaneous copperhistidine appears to have been tolerated best and seems to be the most efficient of the different forms of treatment tried [Sherwood et al, 1989].…”

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Early treatment of Menkes disease with parenteral Cooper-Histidine: Long-term follow-up of four treated patients

Danks²,

et al. 1998

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We report on the long-term clinical course of 4 boys with Menkes disease, treated from early infancy with parenteral copper-histidine, with follow-up over 10-20 years. Three of the 4 had male relatives with a severe clinical course compatible with classical Menkes disease. As a consequence of early treatment, our patients have normal or near-normal intellectual development, but have developed many of the more severe somatic abnormalities of the related disorder, occipital horn syndrome, including severe orthostatic hypotension in 2. In addition, 1 boy developed a previously unreported anomaly, namely, massive splenomegaly and hypersplenism as a consequence of a splenic artery aneurysm. Previously reported molecular studies in 2 of these patients had shown gene defects which would have predicted a truncated and probably nonfunctional gene product. Despite the favorable effects on the neurological symptoms, parenteral copper treatment for Menkes disease should still be regarded as experimental. The development of more effective treatments must await a more precise delineation of the role which the Menkes protein plays in intracellular copper trafficking.

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“…The copper treatment may inhibit neurodegeneration in some patients and prolong survival only if the treatment is initiated prenatally or soon after birth. However, the early treatment is not effective in improving non-neurological impairments such as the connective tissue abnormalities that are associated with reduced activity of lysyl oxidase, a copper-dependent enzyme; as a consequence, early copper therapy usually leads to a milder OHS-like phenotype (Cox, 1999;George and Casey, 2001;Gu et al, 2002;Kodama et al, 2001;Kodama et al, 1999;Royce et al, 1980;Sarkar et al, 1993).…”

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confidence: 99%

A Drosophila model of Menkes disease reveals a role for DmATP7 in copper absorption and neurodevelopment

Bahadorani

Marcon

et al. 2010

Disease Models &Amp; Mechanisms

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SUMMARY Human Menkes disease is a lethal neurodegenerative disorder of copper metabolism that is caused by mutations in the ATP7A copper-transporting gene. In the present study, we attempted to construct a Drosophila model of Menkes disease by RNA interference (RNAi)-induced silencing of DmATP7, the Drosophila orthologue of mammalian ATP7A, in the digestive tract. Here, we show that a lowered level of DmATP7 mRNA in the digestive tract results in a reduced copper content in the head and the rest of the body of surviving adults, presumably owing to copper entrapment in the gut. Similar to Menkes patients, a majority of flies exhibit an impaired neurological development during metamorphosis and die before eclosion. In addition, we show that survival to the adult stage is highly dependent on the copper content of the food and that overexpression of the copper homeostasis gene, metal-responsive transcription factor-1 (MTF-1), enhances survival to the adulthood stage. Taken together, these results highlight the role of DmATP7-mediated copper uptake in the neurodevelopment of Drosophila melanogaster and provide a framework for the analysis of potential gene interactions influencing Menkes disease.

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Copper-histidine therapy for Menkes disease

Cited by 121 publications

References 7 publications

PET Imaging Analysis with ⁶⁴Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model

PET Imaging Analysis with ⁶⁴Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model

Early treatment of Menkes disease with parenteral Cooper-Histidine: Long-term follow-up of four treated patients

A Drosophila model of Menkes disease reveals a role for DmATP7 in copper absorption and neurodevelopment

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Copper-histidine therapy for Menkes disease

Cited by 121 publications

References 7 publications

PET Imaging Analysis with 64Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model

PET Imaging Analysis with 64Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model

Early treatment of Menkes disease with parenteral Cooper-Histidine: Long-term follow-up of four treated patients

A Drosophila model of Menkes disease reveals a role for DmATP7 in copper absorption and neurodevelopment

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PET Imaging Analysis with ⁶⁴Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model

PET Imaging Analysis with ⁶⁴Cu in Disulfiram Treatment for Aberrant Copper Biodistribution in Menkes Disease Mouse Model