A study led by the UAB Institut de Neurociències and published in the journal Nature communications shows in animal models how daily administration of cannabidiol (CBD), a substance obtained from the hemp plant, extends lifespan and improves symptoms associated with Leigh syndrome. This severe mitochondrial disease affecting children is characterized by progressive decline in cognitive and motor functions and early death. The research team also showed in both mice and fibroblasts from children with the disease that CBD improves cell function.
Leigh syndrome is a rare mitochondrial disease that particularly affects the organs and tissues that require the most energy: muscles and the nervous system. It is characterized by progressive neuromuscular decline and early death, and there are currently no approved treatments. That is why it is urgent to find a solution for patients suffering from this disease.
Drs. Emma Puighermanal and Albert Quintana, researchers from the Mitochondrial Neuropathology Laboratory of the Institut de Neurociències at the Universitat Autònoma de Barcelona (INc-UAB), have spent years studying the disease. They seek to understand the processes that cause the dysfunction of mitochondria, the organelles responsible for providing cells with energy, and to find treatments capable of reversing this.
In a study published in Nature communicationsresearchers have now proven that daily CBD administration is a promising treatment option. Through its multiple action it provides antioxidant, anti-inflammatory and antispasmodic effects, which improve symptoms and help restore cellular functions in patients. The study was conducted with two different mouse models of Leigh syndrome, as well as fibroblast cells from patients.
The results revealed that CBD acts at several levels inside the cell, including activating a protein inside the cell’s nucleus known as PPARγ. This protein regulates the expression of many genes involved in immune response, oxidation and mitochondrial function and has been shown to be altered by disease. In addition, CBD increases the expression of the protein metallothionein, which enhances its antioxidant response.
In animal models, cannabidiol administration improved neuropathology in affected brain regions, respiratory abnormalities and social deficits, and also delayed motor decline and neurodegenerative signs. In addition, the treated mice lived significantly longer than the untreated ones. In fibroblast cells from patients, CBD improved their antioxidant processes.
The benefits we observed, together with the safe and well-tolerated profile of CBD, indicate that it is a very promising treatment for patients with Leigh syndrome.”
Dr. Albert Quintana, researcher at INc-UAB and lecturer in the Department of Cell Biology, Physiology and Immunology at UAB
A year ago, researchers received an orphan drug designation for CBD from the European Medicines Agency, which brings many benefits, such as reducing the cost of drug development. “CBD is already approved by the US regulatory body FDA for the treatment of other rare pediatric diseases. We hope that all this will help to translate our results into clinical practices,” concludes Dr. Emma Puighermanal, researcher at INc- UAB and lead author of the article.
The research, designed and coordinated by INc-UAB, also involved the collaboration of the Alicante Neuroscience Institute (UMH-CSIC), the Neuroscience Institute of the University of Barcelona (UBneuro), the Neurocentre Magendie of France and the company Minoryx Therapeutics.
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Journal Reference:
Puighermanal, E., et al. (2024). Cannabidiol ameliorates mitochondrial disease through PPARγ activation in preclinical models. Nature communications. doi.org/10.1038/s41467-024-51884-8.
