Lithium as a possible therapeutic strategy for Cornelia de Lange syndrome

Paolo Grazioli, Chiara Parodi, Milena Mariani, Daniele Bottai, Elisabetta Di Fede, Aida Zulueta, Laura Avagliano, Anna Cereda, Romano Tenconi, Jolanta Wierzba, Raffaella Adami, Maria Iascone, Paola Francesca Ajmone, Thomas Vaccari, Cristina Gervasini, Angelo Selicorni, Valentina Massa

Research output: Contribution to journalArticlepeer-review


Cornelia de Lange Syndrome (CdLS) is a rare developmental disorder affecting a multitude of organs including the central nervous system, inducing a variable neurodevelopmental delay. CdLS malformations derive from the deregulation of developmental pathways, inclusive of the canonical WNT pathway. We have evaluated MRI anomalies and behavioral and neurological clinical manifestations in CdLS patients. Importantly, we observed in our cohort a significant association between behavioral disturbance and structural abnormalities in brain structures of hindbrain embryonic origin. Considering the cumulative evidence on the cohesin-WNT-hindbrain shaping cascade, we have explored possible ameliorative effects of chemical activation of the canonical WNT pathway with lithium chloride in different models: (I) Drosophila melanogaster CdLS model showing a significant rescue of mushroom bodies morphology in the adult flies; (II) mouse neural stem cells restoring physiological levels in proliferation rate and differentiation capabilities toward the neuronal lineage; (III) lymphoblastoid cell lines from CdLS patients and healthy donors restoring cellular proliferation rate and inducing the expression of CyclinD1. This work supports a role for WNT-pathway regulation of CdLS brain and behavioral abnormalities and a consistent phenotype rescue by lithium in experimental models.

Original languageEnglish
Article number34
JournalCell Death Discovery
Issue number1
Publication statusPublished - Jun 2021

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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