2. Academic Validation
  3. Cannabidiol ameliorates mitochondrial disease via PPARγ activation in preclinical models

Cannabidiol ameliorates mitochondrial disease via PPARγ activation in preclinical models

  • Nat Commun. 2024 Sep 4;15(1):7730. doi: 10.1038/s41467-024-51884-8.
Emma Puighermanal 1,  Marta Luna-Sánchez 2 3,  Alejandro Gella 2 3,  Gunter van der Walt 2,  Andrea Urpi 2,  María Royo 4,  Paula Tena-Morraja 5,  Isabella Appiah 2,  Maria Helena de Donato 2,  Fabien Menardy 2,  Patrizia Bianchi 2,  Anna Esteve-Codina 6 7,  Laura Rodríguez-Pascau 8,  Cristina Vergara 9,  Mercè Gómez-Pallarès 2,  Giovanni Marsicano 10,  Luigi Bellocchio 10,  Marc Martinell 8,  Elisenda Sanz 2 3,  Sandra Jurado 4,  Francesc Xavier Soriano 5,  Pilar Pizcueta 8,  Albert Quintana 11 12 13
Affiliations

Affiliations

  • 1 Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. emma.puighermanal@uab.cat.
  • 2 Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain.
  • 3 Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • 4 Institute of Neuroscience, CSIC-UMH, San Juan de Alicante, Spain.
  • 5 Celltec-UB, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
  • 6 Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.
  • 7 Universitat de Barcelona (UB), Barcelona, Spain.
  • 8 Minoryx Therapeutics SL, Barcelona, Spain.
  • 9 Minoryx Therapeutics BE SA, Gosselies, Charleroi, Belgium.
  • 10 Inserm Université de Bordeaux, U1215 Neurocentre Magendie, Bordeaux, France.
  • 11 Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain. albert.quintana@uab.cat.
  • 12 Departament de Biologia Cel·lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, Barcelona, Spain. albert.quintana@uab.cat.
  • 13 Human Metabolomics, Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South Africa. albert.quintana@uab.cat.
PMID: 39231983 DOI: 10.1038/s41467-024-51884-8
Abstract

Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and improves cellular function in fibroblasts from LS patients. CBD delays motor decline and neurodegenerative signs, improves social deficits and breathing abnormalities, decreases thermally induced seizures, and improves neuropathology in affected brain regions. Mechanistically, we identify Peroxisome Proliferator-activated Receptor gamma (PPARγ) as a key nuclear receptor mediating CBD's beneficial effects, while also providing proof of dysregulated PPARγ expression and activity as a common feature in both mouse neurons and fibroblasts from LS patients. Taken together, our results provide the first evidence for CBD as a potential treatment for LS.

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