CBD significantly delayed the onset of seizures and reduced seizure duration in a mouse model of CLN2 disease, a rare and fatal childhood neurodegenerative disorder, according to newly published research.
The study, published in the journal PLOS One, was conducted by researchers from the departments of medicine, pediatrics, neurology and genetics at Washington University in St. Louis. CLN2 disease, previously known as classical late infantile Batten disease, is caused by mutations in the TPP1/CLN2 gene and typically involves developmental delays, epilepsy, progressive neurological decline and early death.
Researchers examined whether long-term treatment with cannabidiol (CBD) could reduce seizures and other symptoms in mice genetically engineered to model CLN2 disease. The animals develop spontaneous seizures as the disease progresses, rather than having seizures artificially induced by drugs, electrical stimulation or other methods commonly used in epilepsy research.
Beginning at approximately one month of age, mice received a daily oral CBD dose of 300 milligrams per kilogram through flavored gelatin cubes. Treatment continued until death for animals being monitored for seizures. A total of 31 mice underwent continuous video and electroencephalography monitoring, with 16 receiving CBD and 15 receiving a vehicle treatment without CBD.
CBD significantly delayed or prevented the animals’ first seizure. The median age at which CBD-treated mice experienced their first seizure was 129 days, compared with 113 days among untreated mice, a delay of 16 days. Researchers noted that the additional 16 days represented nearly 15% of the average lifespan of untreated mice in the study.
Five of the 16 mice receiving CBD never developed a seizure during the study. Three untreated mice also remained seizure-free, although researchers noted that those animals died relatively early compared with the expected lifespan of the disease model.
CBD did not significantly reduce the overall number of seizures experienced by each mouse, but it did significantly reduce average seizure duration when all animals were included in the analysis. When researchers limited the analysis only to mice that experienced at least one seizure, the reduction in seizure duration approached but did not reach statistical significance.
The CBD-treated mice also lived a median of 15 days longer than controls, an increase of about 13%.
Researchers called the reduction in seizure burden notable given that CBD was used alone, without enzyme replacement therapy, gene therapy, anti-seizure medications or other supportive treatments.
The authors said the study provides evidence that chronic oral CBD can have a positive effect on seizures in a model of a severe neurodegenerative disorder and could eventually warrant investigation as an adjunct to existing treatments. They cautioned that the study was relatively small, used only one CBD dose and was conducted in mice, meaning the findings cannot establish that CBD would produce the same effects in children with CLN2 disease.
The research was supported by the Lehrman Family Fund, the Batten Disease Support and Research Association and Washington University in St. Louis.
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