The multiple sclerosis drug, ponesimod, reduces brain inflammation and improves memory, according to a new study in mice and human brain samples.
A team of researchers at the University of Kentucky examined ponesimod (brand name Ponvory), an oral medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsing forms of multiple sclerosis (MS). The findings of the study were published in eBioMedicine.
Ponesimod reduces inflammation in the brain by targeting a specific receptor in the immune system to help regulate the body's response and prevent it from attacking the central nervous system (CNS) — the brain and the spinal cord. This receptor is activated by a lipid called sphingosine-1-phosphate.
The researchers looked at a specific type of cell found in the CNS called microglia. Among other functions, these cells regulate inflammatory responses in the central nervous system.
Dysfunctional microglia are linked to neurodegenerative diseases like Alzheimer's because those cells help clear out the buildup of abnormal protein deposits in the brain — a distinct characteristic of the disease. Those buildups disrupt the communication between the brain's nerve cells and eventually die off.
"The clearance of those proteins is an important target for Alzheimer's disease therapy. In our study, we reprogrammed microglia into neuron-protective cells that clean up toxic proteins in the brain, reduce Alzheimer's neuroinflammatory pathology, and improve memory in the mouse model," said Zhihui Zhu, Ph.D., first-author of the study.
In the study, mice with specific genetic strains expressing the major features of Alzheimer's in their brains were treated with ponesimod. The drug improved attention and working memory in mice with advanced Alzheimer's pathology.
Data collected from tests with human brain models also indicated that ponesimod can be used as a therapy for Alzheimer's.
"Neuroinflammation is a hallmark of Alzheimer's, one of the major causes for disease progression and a promising target for therapy. Our study shows strong experimental evidence that ponesimod may be a therapeutic drug, which not only reduces neuroinflammation but also enhances the clearance of neurotoxic proteins in the brain in middle and late-stage Alzheimer's."- Erhard Bieberich, Ph.D., a professor in the UK College of Medicine
An estimated 6.7 million Americans age 65 and over are living with Alzheimer's disease in 2023. It is a progressive and irreversible neurological disorder where symptoms gradually worsen over years. People with late-stage Alzheimer's disease lose the ability to carry on a conversation and respond to their environment.
Current therapies only help manage symptoms in Alzheimer's patients, they don't cure it. In recent years, the FDA granted accelerated approval for medicines such as Leqembi that slow the progression of Alzheimer's disease by reducing amyloid-beta plaque. However, there are no available medications for patients at the onset and middle stages of the disease.
According to the Alzheimer's Association, 10 early signs of the disease include:
- Memory loss that disrupts daily life, such as forgetting important days or events or asking the same questions over and over.
- Challenges in planning or solving problems. For example, having trouble following familiar recipe or keeping track of monthly bills.
- Difficulty completing familiar tasks, including driving to a familiar location or organizing a grocery list.
- Confusion with time or place, such as losing track of dates, seasons and the passage of time.
- Trouble understanding visual images and spatial relationships. People with Alzheimer's may have difficulty with balance or trouble reading.
- New problems with words in speaking or writing. For example, stopping in the middle of a conversation and not knowing how to continue.
- Misplacing things and losing the ability to retrace steps. People with the disease may put things in unusual places and not be able to find them.
- Decreased or poor judgment, for example, when dealing with money.
- Withdrawal from work, hobbies, social activities, or other engagements.
- Changes in mood and personality, such as increased confusion, suspicion, depression, fear, or anxiety.
The findings show promise in using the multiple sclerosis drug ponesimod for treating Alzheimer's disease as it reduces brain inflammation and improves memory.
- University of Ketucky College of Medicine. UK researchers 1st to show multiple sclerosis drug can be used as Alzheimer’s therapy.
- eBioMedicine. The S1P receptor 1 antagonist Ponesimod reduces TLR4-induced neuroinflammation and increases Aβ clearance in 5XFAD mice.
- Alzheimer’s Association. Alzheimer's Disease Facts and Figures.
- Alzheimer’s Association. Understanding Alzheimer's and dementia.
- Alzheimer’s Association. 10 Early Signs and Symptoms of Alzheimer's and Dementia.