Oral Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Metallothioneins as biomarkers in Menkes disease patients (122150)

Xavier Nel·lo 1 , Melania Mesas 1 2 , Marc Batlle 1 , Anna Guix 1 , Elena Godoy 3 4 , Oscar Palacios 1 , Maria Isabel Pividori 1 2 , Mercè Capdevila 1
  1. Universitat Autònoma de Barcelona, Departament de Química, Cerdanyola del Vallès (Barcelona), Spain
  2. Universitat Autònoma de Barcelona, Institut de Biotecnologia i de Biomedicina (IBB-UAB), Cerdanyola del Vallès (Barcelona), Spain
  3. Málaga Biomedical Research Institute and Nanomedicine Platform, Málaga, Spain
  4. Hospital Regional Universitario, Complex Chronic Children and Palliative Care Unit, Department of Pediatrics, Málaga, Spain

Aims

Menkes disease (MD) is a rare inherited Cu deficiency disorder characterized by progressive neurodegeneration, marked connective tissue abnormalities, steely, sparse hair and death in early childhood. Current MD treatment, which includes parenteral administration of copper-histidine, has resulted largely ineffective. However, the finding that Cu-Elesclomol (Cu-ES) can escort copper to the mitochondria and increase cytochrome c oxidase levels in the brain of a mouse models of MD,1 suggested that Cu-ES could be useful for the treatment of MD patients. As members of the “Copper(Less) Committee” our role is to ascertain if blood plasma concentrations of metallothioneins (MTs) could be used as biomarkers of Cu levels in Menkes patients as the administration of Cu-ES can obviously have beneficial effects but also potentially detrimental ones if certain copper concentration thresholds are exceeded.

 

Methods

MTs are present in virtually all organisms2 and the expression of human MTs is induced by various stressors, including metal ions, endotoxins, cytokines, glucocorticoids, reactive oxygen species, etc. MTs are mainly localized intracellularly, but can also be found extracellularly, and are transported in human blood in which MT concentration could be as low as 10 ng/mL and as high as > 90 ng/mL under some pathological situations. An increased level of MTs has been detected in various liver illnesses, Wilson disease and MD. However, there is still no clinical test available for the determination of MTs in human fluids. We will show the different strategies explored by our team to make MTs determination feasible and compatible with the small volume of blood samples that can be retrieved from our young patients.

 

Results

In early 2022, the Hospital Sant Joan de Déu (Barcelona, Spain), together with the "Menkes International Association”3 and the international “Copper(Less) Committee”, was authorized by the Spanish Medicines Agency to administer exceptional Cu-ES treatment to a 20-month-old boy (MM) with MD. Today, MM has received Cu-ES for more than three years and his clinical symptoms have improved markedly. Other four young boys have been already included in the program and are quickly improving their health conditions.

  1. Gohil, V.M. Expert Opinion on Investigational Drugs, 2021, 30, 1-4.
  2. Capdevila, M.; Bofill, R.; Palacios, Ò.; Atrian, S. Coord. Chem. Rev, 2012, 256, 46-62.
  3. https://menkesinternational.com/