A team of researchers at the University of Kentucky has found that a drug used to treat multiple sclerosis (MS) is potentially effective as a therapy for Alzheimer鈥檚 disease.
Alzheimer鈥檚 is a progressive and irreversible neurological disorder. It鈥檚 estimated 6.2 million Americans aged 65 and older are living with the disease that affects cognitive function, memory and behavior.
鈥淲e stand at the threshold of a critical endeavor to develop new treatment strategies against Alzheimer鈥檚 disease,鈥 said Erhard Bieberich, PhD, a professor in the Department of Physiology in the 好色先生 College of Medicine. 鈥淲e鈥檝e uncovered that a medication already on the market, ponesimod (brand name 鈥楶onvory鈥), can reduce one of the hallmarks of this disease: neuroinflammation.鈥
Bieberich is the principal investigator on a series of grants from the of the and that funded the study. The findings were published in the journal , part of The Lancet Discovery Science in August.
The team studied ponesimod, an oral medication that the U.S. Food and Drug Administration (FDA) has approved to treat relapsing forms of MS. The medication reduces inflammation in the brain by targeting a specific receptor in the immune system to help regulate the body鈥檚 response and prevent it from attacking the central nervous system. This receptor is activated by a lipid termed sphingosine-1-phosphate, the function of which is studied by the Bieberich lab.
鈥淲e are the first to show that ponesimod is effective in a mouse model for Alzheimer鈥檚 disease,鈥 said Bieberich. 鈥淪ince this drug is already in clinical use for therapy of relapsing multiple sclerosis, it is immediately available to be used in Alzheimer鈥檚 disease therapy as well.鈥
好色先生 researchers homed in on a specific type of cell found in the central nervous system called microglia. The cells have several functions in our bodies, including regulating inflammatory responses in the central nervous system 鈥 the brain and the spinal cord.
Dysfunctional microglia are connected to neurodegenerative diseases like Alzheimer鈥檚 because those cells help clear out the buildup of abnormal protein deposits in the brain 鈥 a distinct characteristic of the disease. Those buildups disrupt the communication between the brain鈥檚 nerve cells and eventually die off.
鈥淭he clearance of those proteins is an important target for Alzheimer鈥檚 disease therapy,鈥 said Zhihui Zhu, PhD, first-author of the study and one of the scientists in Bieberich鈥檚 lab. 鈥淚n our study, we reprogrammed microglia into neuron-protective cells that clean up toxic proteins in the brain, reduce Alzheimer鈥檚 neuroinflammatory pathology, and improve memory in the mouse model.鈥
As part of the project, researchers studied mice with specific genetic strains that express the major features of Alzheimer鈥檚 in their brains. They treated half of the mice with ponesimod and measured specific cell activity in the brain. The mice鈥檚 spatial memory was also tested through a maze behavior test.
鈥淭hat 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,鈥 said Zhu. 鈥淥ur tests indicate ponesimod rescues attention and working memory in mice with advanced Alzheimer鈥檚 pathology.鈥
Scientists also worked with 好色先生鈥檚 Alzheimer鈥檚 Disease Research Center within the Sanders-Brown Center on Aging to obtain human brain samples to study. The data collected from those tests were consistent and also indicated ponesimod can be used as a therapy for Alzheimer鈥檚.
鈥淣euroinflammation is a hallmark of Alzheimer鈥檚, one of the major causes for disease progression and a promising target for therapy,鈥 said Bieberich. 鈥淥ur 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鈥檚.鈥
You can read the entire study .