Key Takeaways
- Copper’s involvement in Alzheimer’s is contentious trapped in amyloid plaques (5x higher than normal), it may harm neurons, yet the brain requires it for function. TDMQ20 releases trapped copper, redistributing it without depleting levels.
- In mice, TDMQ20 improved cognitive tasks (maze navigation, object recognition) and slowed behavioral decline but did not reverse dementia. Effects were seen in early and advanced disease models.
- The study bridges opposing views on copper—showing that trapped copper in plaques is harmful, while bioavailable copper is essential.
- TDMQ20 is patented and orally administered, with researchers seeking pharmaceutical partners for human trials. Current Alzheimer’s drugs (e.g., lecanemab) have mixed results, highlighting the need for new approaches.
Chinese scientists have recently developed a molecule that allows the release of the copper trapped in amyloid plaques that is characteristic of Alzheimer’s disease. In mice, they have discovered that using TDMQ20, a Specific Copper Chelator, improved memory performance rather than fully reversing dementia. Specifically, TDMQ20 improved memory performance rather than fully reversing dementia, offering a promising step toward mitigating Alzheimer’s progression.
Alzheimer’s disease, which, affects millions of people worldwide, is the result of a slow degeneration of neurons. Starting in the hippocampus, a brain structure essential to our memory, it eventually spreads through the brain, leading to a loss of memory, bodily functions, and orientation in time and space, gradually limiting the autonomy and cognitive capacities of those affected.
One of the characteristics of this neurodegenerative disease is the presence of amyloid plaques, and extracellular accumulations of protein fragments, in particular Beta-amyloid.
Two researchers from the CNRS Coordination Chemistry Laboratory, together with scientists from Guangdong University of Technology and Shenzhen University, studied the copper present in the brain, especially in amyloid plaques, and its impact on brain degeneration in mice with Alzheimer’s. According to their results, published in the journal ACS Chemical Neuroscience, they were able to inhibit dementia with the help of a molecule that regulates the circulation of this nutrient in the brain.
The role of copper in Alzheimer’s disease, a controversial issue
The role of copper in Alzheimer’s disease is a controversial issue that has been dividing the scientific community for several years: some believe that the accumulation of copper in blood vessels contributes to this degeneration of the brain, while others consider this nutrient to be preventive. Similarly, some studies show a copper deficiency in patients suffering from this disease and therefore the need to increase copper levels, while others point to a copper overload and therefore the need to reduce copper levels.
Metal ions such as copper but also zinc and iron are found in high concentrations in amyloid plaques in the brains of Alzheimer’s patients. These plaques absorb copper: they contain about five times more copper than a healthy brain. The researchers from the study have succeeded in developing TDMQ20 a patented molecule (Copper Chelator) that eases the flow of copper in the brains of mice by releasing the copper trapped in amyloid plaques. Once released, it is brought back into the brain, which, among other things, needs the copper to function.
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Promising results for the future
In the study, the researchers administered the molecule orally to different groups of mouse models: two non-transgenic models mimicking the early stages of Alzheimer’s disease and a transgenic (genetically modified) model representing a more advanced stage of Alzheimer’s disease. In all three cases, the molecule improved mice’s cognitive and behavioral decline due to neurodegeneration when administered over 16 days to improve the cognitive status and for three months to improve behavioral issues. The mice were tested constantly on different tasks to assess their memory and other cognitive functions. The mice were tested in different mazes and also underwent object recognition tests, the latter being particularly effective in assessing the development of declarative memory (the ability to consciously recall facts and events).
Read Also: Exifone Reverses DNA Damage in Mice Suffering From Dementia and Alzheimer’s in MIT Study
This study could lead to advances in medicine for the treatment of neurodegenerative diseases like Alzheimer’s. The CNRS reports that they are looking for a pharmaceutical partner to develop preclinical trials with this drug candidate. As of now, TDMQ20 remains in preclinical stages, but its success in mice has spurred interest in copper-targeted therapies, especially as human trials for other Alzheimer’s drugs like lecanemab show mixed results.
Bottom Line: Bridging Theory and Practice
Feasibility in Humans?
- Promise: TDMQ20’s oral administration and focus on metal ion balance align with trends in neurodegenerative research (e.g., zinc/iron chelators).
- Hurdles: Mouse models don’t fully replicate human Alzheimer’s complexity. Long-term copper modulation risks (e.g., deficiency or toxicity) are unknown.
FAQs
How does TDMQ20 differ from other Alzheimer’s treatments?
Unlike antibody drugs (e.g., lecanemab) that target amyloid plaques directly, TDMQ20 focuses on copper regulation within plaques, potentially normalizing metal ion balance critical for brain function.
Why is copper’s role in Alzheimer’s debated?
Some studies link high copper levels to vascular damage, while others note deficiencies in patients. TDMQ20’s approach of releasing trapped copper rather than removing it offers a middle ground.
When could TDMQ20 reach human trials?
Preclinical development is ongoing. With a pharmaceutical partner, Phase I trials might begin in 3–5 years, pending safety and efficacy validation.
References
Zhao, J., Shi, Q., Tian, H., Li, Y., Liu, Y., Xu, Z., Robert, A., Liu, Q., & Meunier, B. (2020). TDMQ20, a specific copper chelator, reduces memory impairments in Alzheimer’s disease mouse models. ACS Chemical Neuroscience, 12(1), Article 0c00621. https://doi.org/10.1021/acschemneuro.0c00621
