A team of researchers from UPV/EHU’s Neurochemistry and Neurodegeneration group has created a medication that may help reduce memory issues in the early stages of disease in rodent subjects. Research shows that this drug stimulates the cannabinoid neurotransmitter system, which protects brain function, and also improves the cholinergic system—vital for memory and learning—by increasing the levels of acetylcholine, an essential neurotransmitter for these cognitive activities. This discovery is a promising advancement toward new treatment strategies.
Under the direction of Dr. Rafael Rodríguez-Puertas, the Neurochemistry and Neurodegeneration group at UPV/EHU has dedicated over twenty years to exploring new therapies aimed at improving memory for those facing cognitive decline caused by neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Research conducted by Dr. Marta Moreno-Rodríguez brought to light that cannabinoid receptors and specific lipids abundant in choline within the brain play a role in enhancing cognition in rats.
Dr. Rodríguez-Puertas explained, “Through thorough analysis of brain samples from patients at different stages of these diseases, we discovered fascinating results. We observed that when early clinical signs of Alzheimer’s appear, damage occurs in the cholinergic system, essential for memory and learning, while concurrently, the cannabinoid system shows some enhancement.” He also noted that as the disease progresses, the cannabinoid system also becomes affected, indicating its initial protective function against cholinergic impairment to help maintain brain health. Thus, it represents a potential target for therapy.”
In experiments using the drug WIN55.212-2, which targets cannabinoid receptors, the team found that early-stage diseased rodents exhibited performance levels akin to healthy rodents, demonstrating learning and retention of spatial orientation, as highlighted by Dr. Marta Moreno. “It seems that the drug was able to reverse some of the damage or protect the brain from deterioration,” she stated.
An Innovative Approach to Lipid Identification in the Brain
The research team utilized a novel technique developed at UPV/EHU, aimed at identifying and mapping lipids within brain tissue, allowing for insights into cognitive improvement mechanisms. Following treatment, they noted increased activity in the cannabinoid system, improved functionality in damaged cholinergic receptors, and a boost in the synthesis of choline-rich lipids, which are precursors to acetylcholine, the vital neurotransmitter for memory and learning, according to Dr. Rafael Rodríguez. “In simpler terms, we found that cannabinoid receptors were active and acetylcholine levels were rising in the brain. The drug successfully revitalized the cholinergic system and enhanced memory,” Dr. Moreno reported.
Dr. Rodríguez believes that “this drug could potentially be developed into a treatment for alleviating symptoms of dementia, especially in its early stages, because our research indicates that the body attempts to address these issues on its own.” He proposed that “through pharmacological approaches, we could strengthen this natural response, possibly incorporating a combination of cannabinoid medications and acetylcholine precursors.”
Looking for Similar Drugs for Human Trials
Despite the positive outcomes in rodent studies, the team encounters difficulties in progressing with toxicity evaluations and human clinical trials. The main challenge is that WIN55.212-2 is a commonly used compound in research but is not produced by the team, resulting in a lack of commercial viability for pharmaceutical companies, which typically invest significant resources into toxicology and clinical trial phases. Therefore, the team is now focused on identifying and creating new molecules similar to WIN55.212-2 that could garner pharmaceutical interest and facilitate clinical trials. They are working alongside CIC bioGUNE and the University of Vigo on this initiative.
Additional Insights
This research is the culmination of years of rigorous study and represents part of the PhD dissertation by Dr. Marta Moreno-Rodríguez, conducted under the mentorship of Dr. Rafael Rodríguez-Puertas, a leading researcher within UPV/EHU’s Neurochemistry and Neurodegeneration group. Currently, Dr. Moreno is associated with the Barrow Neurological Institute in Arizona, USA.
The brain tissue samples analyzed in this study were sourced from the Basque Biobank, the Central University Hospital of Asturias, and the Barrow Neurological Institute (USA).
