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New Drug Shows Promise in Treating Memory Deficits Linked to Neurodegenerative Diseases
Researchers from the UPV/EHU’s Neurochemistry and Neurodegeneration group have discovered a drug that may effectively address memory deficits in the early stages of neurodegenerative diseases, particularly in rodent models. This drug is noted for its ability to activate the cannabinoid neurotransmitter system, which plays a protective role in the brain, subsequently stimulating the cholinergic system responsible for memory and learning by increasing the production of acetylcholine, a key neurotransmitter.
This significant breakthrough follows over two decades of research led by Dr. Rafael Rodríguez-Puertas and highlights new potential therapies aimed at enhancing cognitive function in individuals suffering from disorders like Alzheimer’s and Parkinson’s. The findings, spearheaded by researcher Dr. Marta Moreno-Rodríguez, indicate that certain cannabinoid family neurotransmitter receptors and specific choline-containing lipids in the brain contribute to cognitive enhancement in rats.
In an illuminating explanation, Rodríguez-Puertas pointed out that extensive analysis of brain tissue from autopsies of patients at various stages of neurodegenerative diseases revealed crucial insights. He noted, “When the first clinical symptoms of Alzheimer’s manifest, damage is observed in the cholinergic system, which is closely tied to memory and learning. Conversely, we observed an increase in activity within the cannabinoid system at this stage.” As Alzheimer’s progresses, however, the cannabinoid system also experiences damage, suggesting it initially responds protectively to cholinergic system degradation.
Testing the efficacy of the drug WIN55.212-2, which engages cannabinoid receptors, the research team found that rodent subjects exhibited behavioral patterns similar to those of cognitively intact animals, demonstrating effective learning and spatial memory retention. Moreno stated, “The drug appears to have reversed or mitigated the damage to the brain.”
A Novel Technique to Identify and Locate Lipids in the Brain
The team used an innovative technique, refined within the UPV/EHU, that allows for the precise identification and anatomical localization of brain lipids. This approach revealed post-treatment enhancements in cannabinoid system activity, increased functionality of damaged cholinergic receptors, and an uptick in the synthesis of choline-containing lipids, which are essential precursors for acetylcholine. According to Rodríguez, this research indicated that “the cannabinoid receptors became activated, leading to elevated acetylcholine levels in the brain, thereby restoring cholinergic function and improving memory.”
Rodríguez holds optimism that this compound could develop into a viable treatment for dementia symptoms, especially at early disease stages. He proposed enhancing the naturally occurring protective mechanisms within the body through pharmacological means, suggesting potential combined therapies utilizing both cannabinoid-based drugs and acetylcholine precursors.
Seeking Similar Molecules to Move on to Clinical Trials
Despite the promising outcomes observed in rodent studies, the path to human clinical trials faces challenges. The research team noted that WIN55.212-2 is a widely used molecule in research that lacks proprietary ownership by any pharmaceutical company, thus complicating potential investment in toxicity studies and clinical trials. To overcome this barrier, the researchers are currently engaged in efforts to identify and develop similar molecules that could attract pharmaceutical interest, facilitating the exploration of this new therapeutic approach. Collaborations with entities like CIC bioGUNE and the University of Vigo are part of these efforts.
Additional Information
This study represents the culmination of years of dedicated research and is based on the PhD thesis of Marta Moreno-Rodríguez, conducted under the mentorship of Rafael Rodríguez-Puertas, a tenured researcher at UPV/EHU. Moreno has since joined the Barrow Neurological Institute in Arizona, USA, contributing to the continuous advancement in this vital research area.
The tissue samples utilized for this comprehensive study were sourced from the Basque Biobank, the Central University Hospital of Asturias, and the Barrow Neurological Institute in the USA.
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