0
0
In a breakthrough study, scientists from the University of the Basque Country (UPV/EHU) have uncovered a promising molecule, WIN55,212-2, that shows the potential to restore cognitive function in the early stages of Alzheimer’s disease. The research, led by Dr. Rafael Rodríguez-Puertas and conducted by the UPV/EHU’s Neurochemistry and Neurodegeneration group, reveals that this cannabinoid-related compound not only protects the brain but also reverses early cognitive damage associated with dementia.
The findings, the result of over two decades of research, open new avenues for therapies aimed at improving memory function in neurodegenerative diseases like Alzheimer’s and Parkinson’s. The study, led by Dr. Marta Moreno-Rodríguez, demonstrated that cannabinoid neurotransmitter receptors and specific choline-containing lipids in the brain enhance cognitive function in rats, providing hope for the treatment of human patients.
Dr. Rodríguez-Puertas explained that extensive analysis of brain tissue from patients at various stages of Alzheimer’s revealed intriguing insights into the disease’s progression. “When the first clinical symptoms of Alzheimer’s appear, damage is found in the cholinergic system, which is responsible for memory and learning,” he said. “But we also observed that the cannabinoid system increases as a response to the damage, trying to protect the brain.”
As the disease progresses, the cannabinoid system becomes compromised. This suggests a potential therapeutic target for intervention. After administering WIN55,212-2 to rodents in the early stages of Alzheimer’s, the researchers observed a striking improvement in their cognitive abilities. “The rodents’ memory and learning abilities returned to normal levels, behaving similarly to healthy animals,” said Dr. Moreno-Rodríguez, noting that the drug seemed to reverse or protect against brain damage.
A key element of this research was the novel technique used by the group to identify and locate lipids in the brain, which allowed them to visualize how the drug increased cannabinoid receptor activity and boosted the synthesis of choline-containing lipids. These lipids are vital in producing acetylcholine, a neurotransmitter essential for memory and learning.
“This molecule could be a game-changer in treating dementia, at least during its early stages,” Dr. Rodríguez-Puertas remarked. “Our research shows that the body already tries to compensate for the damage, and pharmacological treatments could help enhance this effect, or even combine cannabinoids with acetylcholine precursors for greater impact.”
While the results from rodent studies are promising, challenges remain before this molecule can move into human clinical trials. The major hurdle is that WIN55,212-2 is a freely available experimental compound, making it unattractive for pharmaceutical companies that require the potential for commercial exploitation. As a result, the team is working closely with CIC bioGUNE and the University of Vigo to identify similar molecules that could be synthesized and developed into viable therapeutic drugs for human trials.
The study, titled Cognitive improvement via cortical cannabinoid receptors and choline-containing lipids, was published in the British Journal of Pharmacology on November 3, 2024. The research is a result of the PhD thesis of Marta Moreno-Rodríguez, who is now a researcher at the Barrow Neurological Institute in Arizona.
Disclaimer: This study is based on preclinical research conducted in rodents. While the results are promising, further studies, including toxicity assessments and clinical trials, are necessary to determine the safety and efficacy of WIN55,212-2 in human patients.
For more information, refer to the published article: Cognitive improvement via cortical cannabinoid receptors and choline-containing lipids by Marta Moreno-Rodríguez et al., DOI: 10.1111/bph.17381.
