Ponesimod, an MS Drug, Displays Promise as Potential Alzheimer’s Therapy
A recent groundbreaking study, published in the journal eBioMedicine as part of The Lancet Discovery Science series, has unveiled a promising avenue in Alzheimer’s treatment. Researchers from the University of Kentucky have discovered that ponesimod, a medication initially designed for multiple sclerosis (MS), exhibits potential efficacy in combatting Alzheimer’s disease. This development offers hope for those grappling with this progressive neurological disorder that affects cognitive function, memory, and behavior.
Alzheimer’s, a condition characterized by its progressive and irreversible nature, impacts the lives of millions, with an estimated 6.2 million Americans aged 65 and older living with this debilitating disease.
Professor Erhard Bieberich, Ph.D., who holds a prominent position in the Department of Physiology at the UK College of Medicine, emphasized the significance of this discovery: “We stand at the threshold of a critical endeavor to develop new treatment strategies against Alzheimer’s disease. We’ve uncovered that a medication already on the market, ponesimod (known as ‘Ponvory’), can reduce one of the hallmarks of this disease: neuroinflammation.”
Ponesimod, an oral medication approved by the U.S. Food and Drug Administration (FDA) for treating relapsing forms of MS, has demonstrated its ability to alleviate inflammation within the brain. It achieves this by targeting a specific receptor in the immune system, thereby regulating the body’s immune response and preventing it from attacking the central nervous system. This receptor’s activation is governed by a lipid known as sphingosine-1-phosphate, a component meticulously studied by Professor Bieberich’s lab.
Professor Bieberich affirmed the groundbreaking nature of their research: “We are the first to show that ponesimod is effective in a mouse model for Alzheimer’s disease. Since this drug is already in clinical use for the therapy of relapsing multiple sclerosis, it is immediately available to be used in Alzheimer’s disease therapy as well.”
The researchers at the University of Kentucky delved into the realm of microglia, a specific type of cell found in the central nervous system. These cells play multifaceted roles in our bodies, including the regulation of inflammatory responses within the central nervous system—the brain and spinal cord.
Dysfunctional microglia are intricately linked to neurodegenerative diseases like Alzheimer’s. They play a pivotal role in clearing abnormal protein deposits in the brain, a hallmark feature of the disease that disrupts communication between nerve cells and eventually leads to their demise.
Dr. Zhihui Zhu, the first author of the study and a key member of Professor Bieberich’s lab, elaborated on their findings: “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 course of their research, the scientists conducted comprehensive studies on mice with specific genetic strains that manifest the primary characteristics of Alzheimer’s in their brains. Half of these mice were administered ponesimod, allowing the researchers to assess specific brain cell activities. Spatial memory was evaluated through a maze behavior test.
Dr. Zhu elucidated the significance of this 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. Our tests indicate ponesimod rescues attention and working memory in mice with advanced Alzheimer’s pathology.”
The researchers also collaborated with the UK’s Alzheimer’s Disease Research Center within the Sanders-Brown Center on Aging, enabling them to analyse human brain samples. The data derived from these studies consistently reinforced the notion that ponesimod holds promise as an Alzheimer’s therapy.
Professor Bieberich summarised their findings: “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.”
