- READ MORE: A minimal amount of a widely used supplement significantly reduces the risk of dementia
Two medications already authorized by theFDA for cancertherapy could be the solution for reversingAlzheimer’sillness among patients, experts state.
Investigators from the University ofCalifornia, San Francisco (UCSF) believe that letrozole, a hormone-related breast cancer medication, and irinotecan, a chemotherapy drug used for lung and colon cancers, may be beneficialreverse brain damage resulting from an incurable neurodegenerative condition.
In an animal experiment, UCSF specialists discovered that both cancer medications were observed to decrease brain deterioration in mice and also enhance their memory and learning abilities.
Alzheimer’s disease is among the most prevalent types of dementia, typically impacting individuals aged 65 and older. Approximately 7 million people in the United States are affected by this condition, with more than 100,000 deaths reported each year due to it.
It is thought that the condition arises from the formation of harmful amyloid proteins and/or tau proteins in the brain, which may build up and harm cells involved in memory and learning.
Amyloid protein molecules aggregate within brain cells, creating clusters known as plaques. Meanwhile, tau proteins intertwine into thread-like structures referred to as tangles.
Currently, there is no known cure for AD, and only two FDA-approved treatments, Lecanemab (Leqembi) and Donanemab (Kisunla), are available for patients with early-stage Alzheimer’s.
Nevertheless, since letrozole and irinotecan are already authorized for different therapies, this may expedite clinical studies and the possible approval for application in Alzheimer’s patients.
Co-senior author Dr. Marina Sirota, a professor at UCSF, stated: “Alzheimer’s disease involves intricate changes in the brain, making it challenging to research and manage, but our computational methods have created new opportunities to address this complexity directly.”
We are thrilled that our computational method has resulted in a possible combination treatment for Alzheimer’s using already approved FDA drugs.
In individuals with Alzheimer’s disease, the plaques and tangles interfere with the brain’s neurons’ capacity to transmit electrical and chemical signals between each other.
Gradually, this disturbance results in lasting harm to the brain, which contributes to the development of Alzheimer’s and dementia, causing individuals to lose their capacity to communicate, manage personal care, and engage with their surroundings.
Although the specific processes by which Alzheimer’s-related brain damage initiates are still being studied, age and heredity are established risk factors.
Experts also think that elements like a sedentary lifestyle and elevated blood pressure may play a role in the onset of Alzheimer’s.
Although extensive preclinical and clinical research has been conducted, the development of drugs for dementia remains highly challenging, with a 98 percent failure rate in recent years.
Neuroscientist Dr. Yadong Huang, one of the study’s co-authors and a neurology professor at UCSF, stated: ‘Alzheimer’s is probably caused by multiple changes in various genes and proteins that, when combined, affect brain health.’
This poses significant difficulties for drug development – which typically results in one drug targeting a single gene or protein responsible for the illness.
Nevertheless, scientists from USCF think their finding may assist in decreasing or reversing the mental deterioration associated with the condition.
Initially, the group examined how dementia affects gene activity in the brain.
Next, they searched a database containing more than 1,300 medications, such as antipsychotics, antibiotics, antifungals, and chemotherapy drugs, to identify which, if any, reversed any of these gene expressions.
If any currently available medications were discovered to be effective, they could be re-used for treating the condition, thereby shortening the time required to get the drugs to patients.
While searching, the group focused on finding medications that could address the damaging Alzheimer’s-related alterations in neurons and brain cells known as glia, which play a role in supporting the nervous system.
Subsequently, the scientists examined millions of electronic medical records to identify patients who received some of these medications as part of their cancer therapy and assess their risk of developing Alzheimer’s disease.
In the end, they selected letrozole and irinotecan as the most promising options to reduce the likelihood of Alzheimer’s in patients.
By using the two medications in combination, the scientists managed to attack various kinds of brain cells that are impacted by the illness.
They observed that letorozole may mitigate Alzheimer’s impact on neurons, while irinotecan assisted in reversing damage to glial cells.
After testing the combination on mice, researchers observed a notable decrease in harmful tau protein aggregates, and the mice demonstrated enhanced performance in learning and memory tasks.
The researchers involved in the study mentioned that it is still uncertain how the cancer medications manage to reverse the harm.
However, they proposed that letrozole might inhibit the production of estrogen, a hormone that regulates the function of many genes, thereby decreasing the genetic risk of developing Alzheimer’s.
Furthermore, they think that irinotecan might also reduce brain inflammation by inhibiting the fast multiplication and DNA damage of glial cells.
Since this was an animal study, the researchers aim to evaluate the medications in a human clinical trial for Alzheimer’s patients.
Dr. Huang commented on the findings: “Creating a new medication typically requires hundreds of millions, or even billions, of dollars and usually takes over 10 years on average. With this drug that’s being repurposed, it generally only takes two or three years, after which you can proceed to clinical trials with significantly lower costs.”
we have yet to develop or create any highly effective medications that significantly reduce the progression of cognitive decline.
Nevertheless, even with their significant breakthrough, hazards remain since letrozole is recognized for inducing hot flashes in individuals, whereas irinotecan may result in serious diarrhea. Both medications can also cause nausea and vomiting.
Dr. Sirota stated, “These medications come with significant adverse effects, so it’s essential to carefully weigh and determine if those side effects would be manageable for someone suffering from Alzheimer’s. It’s not a straightforward decision.”
The study was featured in the publicationCell.
Read more
