Restoring brain functions in the Mo-blo mouse model of Menkes disease with copper nanoclusters
Menkes disease, caused by ATP7A mutations, leads to severe copper deficiency and fatal neurodegeneration. Current copper-histidine therapy fails to restore brain function. Copper nanoclusters (CuNCs) were designed for their ultrasmall size to cross physiological barriers and deliver copper directly to the whole organism, including the brain. In Mo-blo mice (ATP7A deficient), daily subcutaneous CuNCs markedly improved survival, normalized cuproprotein activities, and restored cognitive and motor functions. Unlike other treatments, CuNCs effectively penetrate the blood-brain barrier, deliver copper to cuproproteins, offering unprecedented neurological rescue. This breakthrough could transform Menkes disease treatment, providing a first-ever therapy for brain copper deficiency. Further clinical development may unlock lifesaving solutions for this rare, fatal disorder.
Authors
- Benjamin Creusot
- Jean‐Marc Alberto (ORCID: https://orcid.org/0000-0002-5126-2890)
- David Coelho (ORCID: https://orcid.org/0000-0001-7010-5789)
- Florent Barbault (ORCID: https://orcid.org/0000-0002-6082-3194)
- Arnaud Wiedemann (ORCID: https://orcid.org/0000-0003-3514-8841)
- Ali Ouadi (ORCID: https://orcid.org/0000-0002-7077-9529)
- Luiz H. G. Tizei (ORCID: https://orcid.org/0000-0003-3998-9912)
- Alexa Courty (ORCID: https://orcid.org/0000-0003-2742-018X)
- Michael Walls
- David Meyre (ORCID: https://orcid.org/0000-0003-4850-7444)
- Benoı̂t Tremblay (ORCID: https://orcid.org/0000-0001-6149-5164)
- Amélia Julien
- Grégory Pourié (ORCID: https://orcid.org/0000-0003-0452-5026)
- Ariane Boudier (ORCID: https://orcid.org/0000-0001-5975-3646)
- Hervé Sartelet (ORCID: https://orcid.org/0000-0002-3183-0125)
- Rémy Umoret (ORCID: https://orcid.org/0000-0001-8591-0721)
- Étienne Derat (ORCID: https://orcid.org/0000-0002-8637-2707)
- Bruno Madebène (ORCID: https://orcid.org/0000-0002-5058-5647)
- Igor Clarot (ORCID: https://orcid.org/0000-0001-9083-601X)
- Pauline Renard
- Justine Paoli (ORCID: https://orcid.org/0009-0000-3247-3863)
- François Feillet (ORCID: https://orcid.org/0000-0002-8717-469X)
- Emma Jung-Rodriguez
- D. Brasse (ORCID: https://orcid.org/0000-0001-5430-8527)
- Laure Brice
- Eric Bremond
- Philippe Arnoux
- Audrey Malardé (ORCID: https://orcid.org/0009-0007-8452-2488)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Universitaire de France (FR)
- Université Paris Cité (FR)
- Université Paris-Saclay (FR)
- Laboratoire de physique des Solides (FR)
- Institut Pluridisciplinaire Hubert Curien (FR)
- Sorbonne Université (FR)
- Laboratoire Réactions et Génie des Procédés (FR)
- Centre Hospitalier Régional et Universitaire de Nancy (FR)
- Interfaces Traitements Organisation et Dynamique des Systèmes (FR)
- Molécule aux Nanos-objets : Réactivité, Interactions et Spectroscopies (FR)
- Cibles thérapeutiques, formulation et expertise préclinique du médicament
- Université Paris 1 Panthéon-Sorbonne (FR)
- Université de Lorraine (FR)
Publication Details
- Journal
- Science Advances
- Published
- 2026-09-30
- DOI
- https://doi.org/10.1126/sciadv.aeg6972
- Primary Topic
- Trace Elements in Health
- Type
- article
- Field-Weighted Citation Impact
- 0.00