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Could the MS drug ponesimod also help treat Alzheimer’s disease? Image credit: alvarez/Getty Images.
  • Millions of people globally have Alzheimer’s disease, for which there is currently no cure.
  • A great deal of research has been focusing on new therapies for the condition.
  • In a study on human brain cells and mouse models of Alzheimer’s, scientists at the University of Kentucky College of Medicine have found that a drug used to treat multiple sclerosis could also be used as a therapy for Alzheimer’s disease.

Millions of people around the world have Alzheimer’s disease, a form of dementia affecting memory and cognition.

With currently no cure for this condition, researchers estimate the number of people globally who have Alzheimer’s will almost double every 20 years.

For this reason, scientists have been placing a great deal of focus on finding new treatment options for Alzheimer’s disease.

Adding to this research is a new study by scientists at the University of Kentucky College of Medicine, who have found that a drug used to treat multiple sclerosis (MS) could also be used as a therapy for Alzheimer’s disease.

This finding is based on research in both mouse models and human brain cells.

The study recently appeared in the journal eBioMedicine, part of The Lancet Discovery Science.

Both MS and Alzheimer’s disease are conditions affecting the central nervous system, which includes the brain.

In the case of MS, the body’s immune system mistakenly attacks the central nervous system, causing inflammation. This inflammation affects nerve fibers, making it difficult for electrical messages from the brain to reach other areas of the body.

The main symptoms of MS include muscle weakness, numbness in the face and limbs, and mobility problems. However, people with MS may also experience cognitive impairment symptoms similar to those associated with Alzheimer’s disease, including memory loss, learning difficulties, and trouble multitasking.

Although scientists are still unclear what exactly causes Alzheimer’s disease, previous research shows inflammation within the brain may damage neurons and brain cells, leading to the condition.

While the main symptoms of Alzheimer’s include memory loss and cognitive deficits, a person with the disease can also experience mobility issues similar to those in MS, including balance and coordination problems. As the disease advances, people with Alzheimer’s disease may lose the ability to stand, walk, and eat.

A study in June 2023 found people with MS are at a higher risk for developing any type of dementia, including Alzheimer’s disease for which they found the risk to be twice as high.

Another study also published in June 2023 presented evidence that MS and Alzheimer’s disease are connected by sharing a common environmental factor, such as a viral infection, and the loss of the myelin sheaths that protect nerve fibers, which is known as demyelination.

For this study, researchers focused on a drug called ponesimod — under the brand name Ponvory — that is approved by the Food and Drug Administration (FDA) to treat MS.

“Ponesimod inhibits a specific cell signaling pathway that induces neuroinflammation in multiple sclerosis,” Dr. Erhard Bieberich, a professor in the Department of Physiology at the University of Kentucky College of Medicine and lead author of this study explained to Medical News Today. “We reasoned that ponesimod would also inhibit neuroinflammation in Alzheimer’s disease.

Dr. Bieberich and his team targeted a specific type of cell found in the central nervous system called microglia.

One of the many functions of microglia includes regulating inflammatory responses in the central nervous system. According to researchers, dysfunctional microglia have been linked to neurodegenerative diseases, such as Alzheimer’s.

“Neuroinflammatory microglia fail to remove amyloid. In turn, amyloid accumulates and damages neurons in Alzheimer’s disease. Reprogramming microglia with ponesimod restores their clearance function and reduces amyloid, which then prevents neuronal damage in Alzheimer’s disease.”

– Dr. Erhard Bieberich

To test their hypothesis about ponesimod, Dr. Bieberich and his team used a mouse model of Alzheimer’s disease. The mice had specific genetic strains that expressed the major features of Alzheimer’s in their brains.

Half of the mice were treated with ponesimod. Scientists measured specific cell activity in their brains and also tested their spatial memory through a maze behavior test.

Upon analysis, the researchers found the mice treated with ponesimod had a better attention span and working memory than non-treated mice.

Additionally, the scientists tested their theory on human brain samples, finding data collected from both tests were consistent and showed ponesimod could be used as an Alzheimer’s therapy.

“We found that ponesimod reduces amyloid plaques in areas of the brain responsible for attention and memory,” Dr. Bieberich explained. “Testing these functions confirmed that cognition is improved as well. However, there is never certainty that reducing amyloid leads to improved cognition unless it is shown by the appropriate tests.”

“Drugs that prevent or reduce neuroinflammation work best when given early in the disease process,” he continued. “In our next experiments, we will define the optimal time point to prevent Alzheimer’s disease with ponesimod. In [the] future, we hope to contribute to clinical trials testing the benefits of ponesimod in Alzheimer’s disease therapy.”

MNT also spoke with Dr. Santosh Kesari, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, and regional medical director for the Research Clinical Institute of Providence Southern California, about this study.

“I think this is exciting as it’s becoming increasingly clear that Alzheimer’s and other neurodegenerative conditions are really rooted in inflammation and immune dysfunction in the brain as the cause of the disease or promoting the symptoms of the disease,” he said when asked about his first reaction to the study findings.

“This study really backs that up even more so from [identifying] a potential treatment opportunity to address the abnormal inflammation that causes Alzheimer’s and other diseases,” added Dr. Kesari.

“Besides multiple sclerosis, Alzheimer’s, Parkinson’s, ALS, and other neurodegenerative diseases may also have inflammation as a key component of the damage to the brain,” he continued.

“And so we can learn a lot from multiple sclerosis and the drugs that are used to control the inflammation there and pivot them to be used in the context of other diseases where inflammation may not be as great as multiple sclerosis, but still relevant in causing some of the symptoms of the disease,” said Dr. Kesari.