An existing medication for multiple sclerosis could possibly be retooled into a treatment for Alzheimer’s disease, new research suggests. A team of scientists has found evidence in mice and human brain tissue that the drug ponesimod can reduce the inflammation and toxic amyloid plaques found in those with Alzheimer’s. More research will be needed to test out this theory, however.
The research was conducted by scientists from the University of Kentucky. They theorized that a particular receptor found in brain cells called microglia might play a role in Alzheimer’s and possibly other neurodegenerative diseases.
Among their many functions, microglia help regulate the brain’s immune response and clear out toxic waste. One of these toxins is an abnormal form of the protein amyloid beta. In people with Alzheimer’s, this abnormal amyloid beta builds up in the brain, eventually turning into hardy clumps called plaques. Research has suggested that healthy microglia can help prevent this accumulation from happening, while the development of Alzheimer’s can induce the production of dysfunctional microglia that can harm our brains in various ways, including through increased inflammation.
The team’s earlier work has suggested that abnormal amyloid beta might negatively influence microglia cells through a receptor called sphingosine-1-phosphate (S1P) transporter spinster 2, or Spns2. So they wanted to see if they could block the process by using a drug already known to inhibit this receptor, the recently approved MS medication ponesimod.
They experimented with mice bred to develop Alzheimer-like illness as well as with human samples of microglia cells. In both cases, the ponesimod appeared to work as hoped. It seemed to reduce the inflammation caused by microglia, while improving their ability to clear rogue amyloid from the brain. Perhaps most importantly, mice treated with ponesimod performed better on memory tests than controls, indicating that the drug could potentially slow or stop Alzheimer’s symptoms.
“The clearance of those proteins is an important target for Alzheimer’s disease therapy,” said lead author Zhihui Zhu in a statement from the university. “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.”
The study’s findings were published last month in the journal eBioMedicine.
Of course, mice and lab experiments are only the starting point for showing that a treatment could do the same in human patients. Since ponesimod is already used for MS, that could speed up the process of studying its use in Alzheimer’s disease. The authors also note that there are no currently approved drugs that increase the clearance of amyloid by microglia. So the work done here could very well lead to a new mechanism for treating Alzheimer’s down the road.
In recent years, there have been several approvals of drugs that reduce amyloid plaques in those with Alzheimer’s. These drugs are expected to have a modest effect at best on people’s symptoms for the time being. But a combination of different treatment approaches might someday lead to substantial improvements in people’s prognosis, experts have hoped.