A study by the University of the Basque Country (UPV/EHU) demonstrates that the drug WIN55,212-2 protects the brain and reverses early cognitive damage caused by dementia, while also explaining its mechanism of action.
Over two decades of research conducted by the Neurochemistry and Neurodegeneration group at UPV/EHU, led by Dr. Rafael Rodríguez-Puertas, has uncovered a promising pathway for developing therapies aimed at improving memory in cases of cognitive impairment caused by neurodegenerative diseases like Alzheimer’s and Parkinson’s.
A study by Dr. Marta Moreno-Rodríguez within the group demonstrated that cannabinoid neurotransmitter receptors and specific choline-containing lipids in the brain play a role in enhancing cognitive function in rats.
The researcher Rodríguez-Puertas explained that “analyses carried out over the years on a very large sample of brain tissue from autopsies of patients who were at different stages of development of the disease enabled us, intriguingly, to see that when the first clinical symptoms of Alzheimer’s emerge, damage is found in the area that is initially affected in patients and is caused by one of the interneuronal transmission systems, the cholinergic system (which controls memory and learning and uses acetylcholine as a neurotransmitter); by contrast, we saw that another neurotransmission system, the cannabinoid system, increases.”
The team also found that as the disease progresses, the cannabinoid system also ends up damaged: “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 said. “It is therefore a therapeutic target on which to act.”
After testing the effect of the drug WIN55.212-2, which interacts with cannabinoid receptors, on rodents in the early stages of the disease, the team found “that they behaved in the same way as those without brain damage: they learned and remembered spatial orientation in the same way,” explained Marta Moreno. “You could say that in some way the drug reversed the damage or protected the brain.”
A novel technique to identify and locate lipids in the brain
The research group was able to understand the mechanism of this cognitive improvement “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,” explained Rafael Rodríguez.
In other words, “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 suggested.
Seeking similar molecules to move on to clinical trials
Although the results of the tests on rodents were very promising, and the next step would be to study their toxicity and move on to clinical testing on humans, the research team has come up against the obstacle that the molecule is a free-to-use molecule.
In other words “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 are now working to find and synthesize molecules similar to WIN55.212-2 that could be of interest to the pharmaceutical industry and thus pave the way towards the clinical study of this new therapeutic pathway.
To this end, they are working in collaboration with CIC bioGUNE and the University of Vigo.
Additional information
This study is the outcome of many years of uninterrupted work and of the PhD thesis of the researcher Marta Moreno-Rodríguez, written up under the supervision of Rafael Rodríguez-Puertas, a tenured doctoral researcher and leader of the UPV/EHU’s Neurochemistry and Neurodegeneration research group. Marta Moreno is currently working at the Barrow Neurological Institute in Arizona (USA).
The tissue samples analyzed over the years came 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
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22 Comments
This discovery is potentially too important to abandon. It could easily be funded by the pooled resources of developed nations. It could then be widely available to people throughout the world. Alternatively, the drug could cost thousands of dollars and become nothing more than a source of profits for investors.
As usual profits before people.
So very sad that there is a molecule they have available that seems to work, but they have to find something pharmaceutical companies can make big money on just to get funded to further research. Meanwhile, families get to watch their loved ones disappear then die with this HORRIBLE disease. So disgusting that profit is more important than people.
This is the sort of thing that could/should be funded by public health institutions – studies of non-patentable molecules that will potentially produce affordable therapies!
But it will take 100 years of lawsuits deciding what pharmaceutical company and their investors to manufacture the drug in China for pennies so big pharma and their lawyers can make trillions, yea!
It’s disgusting reading how they hault this project over their profit. Where is our government looking over this cure as a public benefits. Not big pharma.
Do you understand this is not USA but Spain and Spaniards scientists making this decision. Stop the hate
It may not be the USA but it is still because of big drug companies wanting to make money and I can tell you investors probably will be from US.. It isn’t hate. It is disgust because after watching my wonderful Mom disappear before me for 7 years, and having no way to truly help her, is the most awful pain. So what an awful thing that it ALWAYS comes down to how much money can be made off of people suffering.
There must be some way for “the people ” to have some solid medical advance(s ) representation with enough solid ethical foundation with financial backing .
This info was discovered about 27yrs back, at UC Berkley, when a team was testing the affects THC, CBDs & general cannabinoids had on the brain. They figured out (saw evidence in their experiments) that people who consumed Marijuana daily were 36% less likely to develop a neuro-degenerative disease. This was due to there being a thickening of the neuro-receptors (in the Cannabinoid receptor region) in the brain, from the constant assault from THC. It basically forms a callus, that protects it from cell damage. That’s why people who consume weed products daily/constantly have short-term memory issues. The “callus” makes it harder to receive the neurotransmitter signals, so more have to be transmitted in order for them to be received. Look into that study, it’ll blow your minds. All of this info would be common knowledge if the damn feds would’ve made Marijuana chem testing legal & readily accessible decades ago.
Don’t know what this world coming too ,all these companies are interesting in is making money…
People don’t matter anymore it’s disgusting,I wish for a cure and to have my husband back..it’s devastating .
Do you understand this is not USA but Spain and Spaniards scientists making this decision
Keep me informed.
Never mind Mars;I just want injured brains 🧠 repair work done ✔️ 👍 as well as cure for all brain 🧠 disorders
Please keep us updated!!
I’d give almost anything to have my brain the way it was before Lyme got to and destroyed aprox 30% of it,most noticeable with my memory. Before Lyme,my memory used to be so good,I used to ~wish~ I could forget things,after Lyme, I honestly can’t remember anything,it hurts so much when my family talks about things and I honestly can’t remember anything about what they’re talking about. I would honestly volunteer to be a human subject,if it meant even a slim chance of getting my brain/memory healed/working again. Worst case scenario,doesn’t help me,but maybe it would help the researchers figure a way to help others.
Hear is a boil on the arse of humanity.
So (let me get this straight) they are abandoning research into a promising treatment for a terrible condition that uses a molecule in the public domain, and are concentratiing instead on looking for another molecule that’s similar but different enough to be patentable?
Obviously that’s a disgrace, to put it very mildly..
Are there no not-for-profit organisations to take it up???
The pharmaceutical companies did the same thing with Marinol. It is a medicine that is used to enhance appetite for certain patients such as ones receiving chemo. This medicine contains THC, the active ingredient in Marijuana, that technically can be grown at home for free. However big pharma can not make a profit that way!! Sooo they developed a lab developed synthetic form of THC, and charge dollars for it! This medicine has been around for decades, all while our federal government has claimed that there is no medical use for Marijuana. It’s all about the money.
Do you understand this is not USA but Spain and Spaniards scientists making this decision
…there used to be safeguards in American society built into the regulatory framework. For instance, the FCC has regulations about providing and testing periodically the Emergency Broadcasting Network system to provide citizens information in an emergency. There used to be guidelines for providing public service messaging as part of the licenses to broadcast. There used to be an inference of truth in broadcasting on the networks as well. Fox obliterated that.
–my point here, there shoud be a mandated onus on altruistic research–the US government invented the internet, right? Why aren’t they taking up these causes on a more open and expansive basis? Wouldn’t it benefit the population AND the country in the long run? Just asking…
Why are you referencing America? The research was conducted in Spain and if I recall correctly, there are pharmaceutical companies based outside of America. Perhaps the World Health Organization should fund further development as a global initiative, eh?
We voted for the party whose main goals are corporate profits & making America great again. This mean less regulations & altruistic efforts being funded. We wanted this!