Scientists Discover Promising Molecule That Restores Cognitive Function in Early Alzheimer’s
A examine by the University of the Basque Country (UPV/EHU) demonstrates that the drug WIN55,212-2 protects the mind and reverses early cognitive harm brought on by dementia, whereas additionally explaining its mechanism of motion.
Over twenty years of analysis carried out by the Neurochemistry and Neurodegeneration group at UPV/EHU, led by Dr. Rafael Rodríguez-Puertas, has uncovered a promising pathway for growing therapies geared toward enhancing reminiscence in circumstances of cognitive impairment brought on by neurodegenerative ailments like Alzheimer’s and Parkinson’s.
A examine by Dr. Marta Moreno-Rodríguez throughout the group demonstrated that cannabinoid neurotransmitter receptors and particular choline-containing lipids in the mind play a job in enhancing cognitive operate in rats.
The researcher Rodríguez-Puertas defined that “analyses carried out over time on a really massive pattern of mind tissue from autopsies of sufferers who have been at completely different levels of growth of the illness enabled us, intriguingly, to see that when the primary scientific signs of Alzheimer’s emerge, harm is discovered in the world that’s initially affected in sufferers and is brought on by one of many interneuronal transmission programs, the cholinergic system (which controls reminiscence and studying and makes use of acetylcholine as a neurotransmitter); against this, we noticed that one other neurotransmission system, the cannabinoid system, will increase.”
The group additionally discovered that because the illness progresses, the cannabinoid system additionally finally ends up broken: “It’s as if this cannabinoid system has an initial protective response to the damage of the cholinergic system and tries to protect the brain,” he stated. “It is therefore a therapeutic target on which to act.”
After testing the impact of the drug WIN55.212-2, which interacts with cannabinoid receptors, on rodents in the early levels of the illness, the group discovered “that they behaved in the same way as those without brain damage: they learned and remembered spatial orientation in the same way,” defined Marta Moreno. “You could say that in some way the drug reversed the damage or protected the brain.”
A novel approach to establish and find lipids in the mind
The analysis group was capable of perceive the mechanism of this cognitive enchancment “by using a novel technique developed and fine-tuned by the research group at the UPV/EHU and which enables the lipids in the brain to be identified and anatomically located. That way we saw that, after treatment, the activity of the cannabinoid system had increased; and also that there was an increase in the activity of the patients’ cholinergic neuronal receptors that had been damaged, and also that there was an increase in the synthesis of certain lipids containing choline, which are precursors of acetylcholine, a neurotransmitter that controls memory and learning in the brain,” defined Rafael Rodríguez.
In different phrases, “the cannabinoid receptors were seen to be activated and the acetylcholine levels in the brain to be increased. The drug restored the cholinergic system and improved memory,” added Moreno.
Rafael Rodríguez believes that “this molecule could become a drug to treat the symptoms of dementia, at least during the initial stages of the disease, because we have already seen that the body itself, physiologically, tries to do something similar.”
“With these pharmacological treatments we could help to enhance that effect, or perhaps even apply a mixed treatment of cannabinoid drugs with acetylcholine precursors,” he recommended.
Seeking comparable molecules to maneuver on to scientific trials
Although the outcomes of the assessments on rodents have been very promising, and the following step can be to check their toxicity and transfer on to scientific testing on people, the analysis group has come up towards the impediment that the molecule is a free-to-use molecule.
In different phrases “it is a synthesis molecule that is widely used in experimentation; we did not synthesize it ourselves. It is not a molecule that a particular pharmaceutical company can exploit. Toxicology studies and clinical trials constitute a major investment for the pharmaceutical industry and this molecule does not offer them the possibility of future commercial exploitation”; so they’re now working to seek out and synthesize molecules much like WIN55.212-2 that could possibly be of curiosity to the pharmaceutical business and thus pave the best way in direction of the scientific examine of this new therapeutic pathway.
To this finish, they’re working in collaboration with CIC bioGUNE and the University of Vigo.
Additional info
This examine is the end result of a few years of uninterrupted work and of the PhD thesis of the researcher Marta Moreno-Rodríguez, written up underneath the supervision of Rafael Rodríguez-Puertas, a tenured doctoral researcher and chief of the UPV/EHU’s Neurochemistry and Neurodegeneration analysis group. Marta Moreno is presently working on the Barrow Neurological Institute in Arizona (USA).
The tissue samples analyzed over time got here from the Basque Biobank, the Central University Hospital of Asturias, and the Barrow Neurological Institute (USA).
Reference: “Cognitive improvement via cortical cannabinoid receptors and choline-containing lipids” by Marta Moreno-Rodríguez, Jonatan Martínez-Gardeazabal, Iker Bengoetxea de Tena, Alberto Llorente-Ovejero, Laura Lombardero, Estibaliz González de San Román, Lydia Giménez-Llort, Iván Manuel and Rafael Rodríguez-Puertas, 3 November 2024, British Journal of Pharmacology.
DOI: 10.1111/bph.17381
