Drug Helps Reverse Alzheimer’s Symptoms In Experiments
Alzheimer’s is one of the main causes of dementia in the world, affecting millions of people and causing a progressive deterioration in memory, thinking and cognitive abilities. Despite decades of research, current treatments are limited to reducing some symptoms and slowing the progression of the disease, without achieving significant reversal of damage. Existing drugs attack amyloid plaques in the brain, the main markers of Alzheimer’s, but fail to improve cognitive function.
A recent study in mice with Alzheimer’s has revealed an innovative approach: restore brain metabolism to reverse some symptoms of the disease. Researchers have found that an experimental drug blocks a key enzyme and allows mice to regain their ability to learn and remember. This discovery suggests that treating the brain’s energy deficit could be the key to improving the quality of life of those suffering from Alzheimer’s, opening new avenues in the search for treatments.
In this article, we will discuss the main findings of this research.
The brain is the most demanding organ of the human body in terms of energy expenditure.since it requires large amounts of glucose to maintain its functions, such as learning, memory, and information processing. In a healthy person, brain cells, especially neurons, depend on a constant supply of energy to communicate with each other and keep the mind active and alert.
However, in people with Alzheimer’s, especially of older ages, this energy machinery begins to fail. One of the main markers of the disease is the accumulation of amyloid protein plaques and tau tangles, which interfere with neuronal communication. These toxic structures not only damage neurons, but also affect other key cells in the brain, such as astrocytes, responsible for helping provide energy for neurons.
The result is a brain with less and less energy, which leads to a gradual loss of cognitive function, including memory and the ability to carry out daily, everyday tasks. This energy depletion is one of the main problems in Alzheimer’s and contributes to the progression of symptoms.
Despite advances in the treatment of the disease, current drugs focus on eliminating amyloid plaques, but do not directly address the problem of energy deficit in the brain. This has led scientists to investigate new approaches that seek to restore brain energy and, consequently, improve cognitive functions affected by the disease.
The metabolic approach: a paradigm shift
The discovery that brain metabolism plays a key role in the development of Alzheimer’s has opened a new focus and debate around treatment research. Traditionally, efforts have focused on combating amyloid plaques and tau tangles, but these have failed to reverse symptoms. Now, scientists are exploring how to improve the brain’s metabolism, with the primary goal of restoring the energy needed for neurons to function properly.
This approach focuses on cells called astrocytes, which, as we have already mentioned, are essential for providing energy to neurons. Under normal conditions, astrocytes transform nutrients, such as glucose, into lactate, which is later used by neurons for energy. However, In Alzheimer’s, the levels of an enzyme called IDO1 increase and astrocytes thus stop fulfilling their energy support function..
Stanford researchers, by eliminating this enzyme in Alzheimer’s mice, found that astrocytes resumed their task of supplying energy to neurons. This change allowed the neurons to recover their learning and memory capacity. Blocking IDO1 not only prevented energy depletion, but also awakened astrocytes from their sleepy state, returning them to their essential role in the brain.
This finding marks a paradigm shift, suggesting that restoring metabolic function in the brain could be an effective strategy to treat Alzheimer’s, something that current treatments fail to do.
The study of mice with dementia and the drug that reverses the symptoms
The experiment that led to the discovery of the new metabolic approach in the treatment of Alzheimer’s began unexpectedly. A team of researchers at Stanford University was studying the enzyme IDO1, known to regulate cellular metabolism. Their initial hypothesis was that by eliminating this enzyme in Alzheimer’s mice, brain metabolism would deteriorate further. Surprisingly, the opposite happened: Mice without the IDO1 enzyme showed a significant improvement in their ability to convert glucose into energy and did not experience the memory loss associated with the disease.
Intrigued by these results, the scientists delved deeper into the research and discovered that by suppressing the enzyme, astrocytes in the brain regained their ability to provide energy to neurons. Astrocytes, which usually become inactive when amyloid plaques begin to appear in the brain, were “awakened” by eliminating IDO1, allowing the neurons to resume their learning and memory function.
To confirm these findings, the team used an experimental drug, originally designed to fight cancer, that blocks the activity of the IDO1 enzyme. This drug was administered to mice with Alzheimer’s, and the results were equally impressive. Mice treated with this drug were able to learn to escape from situations in a test environment, as healthy mice would do.. This showed a clear restoration of cognitive function, something that had not been achieved with treatments that only remove amyloid plaques.
Furthermore, when the scientists analyzed the brains of the treated mice, they found that glucose metabolism had normalized in key areas such as the hippocampus, responsible for memory. Remarkably, this improvement occurred even in cases where Alzheimer’s plaques and tangles were still present in the brain, underscoring the importance of this metabolic approach.
Implications for the treatment of Alzheimer’s
This discovery opens a new door in the treatment of Alzheimer’s by demonstrating that improving brain metabolism can reverse some of the most debilitating symptoms of the disease. Unlike current treatments, which focus on removing amyloid plaques without improving cognitive function, this metabolic approach seeks to reactivate supporting cellslike astrocytes, to restore brain energy.
While current medications, such as Lecanemab and Donanemab, have been successful in reducing plaque buildup, they have not shown significant effects on memory or thinking. However, the experimental drug we are talking about that blocks the IDO1 enzyme has managed to wake up astrocytes and allow neurons to function more efficiently again, improving learning and memory capacity in mice.
This approach could be complementary to existing treatments, combining the removal of amyloid plaques with the restoration of brain metabolism. Additionally, by focusing on astrocytes and other supporting cells rather than just neurons, it presents a more comprehensive view of Alzheimer’s as a disorder of the entire brain system, offering new hope for improving patients’ quality of life.
Limitations and next steps
Although the results of the study in mice that we have mentioned are promising, it is important to also recognize the limitations they imply before considering their application in human subjects.
1. Animal models
The experiments carried out so far have focused exclusively on mice with Alzheimer’s, and although their brain system is known for its similarities with that of humans, it is not identical, and the effect of this drug cannot be assumed to be equivalent. Treatments that work in animal models do not always produce the same effects in people.
2. Clinical trials
The crucial next step will be to conduct clinical trials in humans to determine whether the drug that blocks the IDO1 enzyme can generate the same metabolic and cognitive benefits. These trials will need to evaluate not only the effectiveness of the treatment, but also its long-term safety, since this drug was originally designed to fight cancer, which could have unforeseen side effects.
3. Amyloid plaques and tau tangles
Another limitation is that this experimental drug does not yet appear to eliminate amyloid plaques or tau tangles, which are still present in the brains of treated mice. Although the drug does improve memory and thinking, it is not clear whether it would be enough to stop the progression of the disease in the long term. Still, these findings suggest a new path in the search for more effective and potentially more comprehensive treatments for Alzheimer’s.
