Researchers from the University of Kentucky have discovered that a drug used for multiple sclerosis treatment may be a potential treatment for Alzheimer's disease, affecting over 6.2 million Americans aged 65 and older.

“We stand at the threshold of a critical endeavor to develop new treatment strategies against Alzheimer’s disease,”

said Erhard Bieberich, Ph.D., a professor in the Department of Physiology in the UK College of Medicine. “We’ve uncovered that a medication already on the market, ponesimod (brand name ‘Ponvory’), can reduce one of the hallmarks of this disease: neuroinflammation.”

A study published in eBioMedicine examined ponesimod, an FDA-approved oral medication for relapsing MS, which targets an immune receptor triggered by sphingosine-1-phosphate to reduce brain inflammation.

“We are the first to show that ponesimod is effective in a mouse model for Alzheimer’s disease,” said Bieberich. “Since this drug is already in clinical use for therapy of relapsing multiple sclerosis, it is immediately available to be used in Alzheimer’s disease therapy as well.”

UK researchers studied microglia, a central nervous system cell that regulates inflammatory responses in the brain and spinal cord. Dysfunctional microglia are linked to neurodegenerative diseases like Alzheimer's, as they clear abnormal protein deposits in the brain, disrupting nerve cell communication and leading to cell death.

“The clearance of those proteins is an important target for Alzheimer’s disease therapy,” said Zhihui Zhu, Ph.D., first-author of the study and one of the scientists in Bieberich’s lab. “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.”

In the study, researchers examined Alzheimer’s-like mice with specific genetics, administering ponesimod to half and assessing brain cell activity and spatial memory using a maze test.

“That specific test is a measure of the spontaneous tendency of the mice to alternate their free choices to enter the two arms of the maze,” said Zhu. “Our tests indicate ponesimod rescues attention and working memory in mice with advanced Alzheimer’s pathology.”

Scientists from the UK's Alzheimer's Disease Research Center have obtained human brain samples, suggesting ponesimod as a potential Alzheimer's therapy.

“Neuroinflammation is a hallmark of Alzheimer’s, one of the major causes for disease progression and a promising target for therapy,” said Bieberich. “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.”