A study led by the Autonomous University of Barcelona (UAB) has demonstrated in animal models that daily administration of cannabidiol (CBD), a substance obtained from the cannabis plant, extends lifespan and improves symptoms associated with Leigh syndrome. The research group also demonstrated that CBD improves cell function in both mice and in fibroblasts from children with the disease.
Leigh syndrome is a rare pediatric mitochondrial disorder that specifically affects the organs and tissues that need the most energy: muscles and the nervous system. It is characterized by progressive neuromuscular deterioration and premature death and there is currently no approved treatment, which explains the urgent need to find a solution for patients suffering from this disease.
Dr. Emma Puigelmanal and Dr. Alberto Quintana from the UAB Neuroscience Institute have been studying the disease for years. They are trying to understand the processes that cause the dysfunction of mitochondria, the organelles responsible for providing energy to cells, and find treatments that can reverse this.
Now, a study published in Nature Communications has demonstrated that daily administration of CBD is a promising treatment option. CBD's diverse actions provide antioxidant, anti-inflammatory and anticonvulsant effects, improving patients' symptoms and helping restore cellular function. The study was carried out using two different Leigh syndrome mouse models and fibroblast cells from patients.
Results revealed that CBD acts at multiple levels within the cell, activating a protein in the cell nucleus called PPARγ. This protein controls the expression of many genes involved in immune response, oxidation, and mitochondrial function, and is found to be altered in disease. Additionally, CBD increases the expression of metallothionein proteins, enhancing antioxidant responses.
In animal models, cannabidiol administration improved neuropathology in affected brain regions, respiratory abnormalities, and social impairments, and delayed motor decline and signs of neurodegeneration. Moreover, treated mice lived significantly longer than untreated mice. In patient fibroblasts, CBD improved antioxidant processes.
“The benefits we have observed, combined with the safety and tolerability of CBD, make it a truly promising treatment for patients with Leigh syndrome,” Quintana said.
A year ago, the researchers received orphan drug designation for CBD from the European Medicines Agency, which has many benefits, including reducing drug development costs. “CBD is already approved by the US regulator, the FDA, for the treatment of other rare pediatric diseases. We hope that all this will help translate our findings into clinical practice,” says Puigelmanal.
Image caption: A 3D representation showing the action of cannabidiol molecules in neuronal mitochondria. Image ©INc-UAB.
