New Delhi :A drug used to treat cancer may also limit the effects of Alzheimer’s disease, a new study conducted in mice has found. Scientists from University of California (UCI) in the US used the drug to disarm the brain’s response to the distinctive beta-amyloid plaques that are the hallmark of Alzheimer’s disease.
They found that flushing away the abundant inflammatory cells produced in reaction to beta-amyloid plaques restored memory function in test mice.
The study showed that these cells, called microglia, contribute to the neuronal and memory deficits seen in this neurodegenerative disease.
“Our findings demonstrate the critical role that inflammation plays in Alzheimer’s-related memory and cognitive losses,” said Kim Green from UCI.
Researchers treated Alzheimer’s disease model mice with a small-molecule inhibitor compound called pexidartinib, or PLX3397, which is currently being used in several phase 2 oncology studies and a phase 3 clinical trial to treat a benign neoplasm of the joints.
The inhibitor works by selectively blocking signalling of microglial surface receptors, known as colony-stimulating factor 1 receptors, which are necessary for microglial survival and proliferation in response to various stimuli, including beta-amyloid.
This led to a dramatic reduction of these inflammatory cells, allowing for analysis of their role in Alzheimer’s.
Researchers noted a lack of neuron death and improved memory and cognition in the pexidartinib-treated mice, along with renewed growth of dendritic spines that enable brain neurons to communicate.
Although the compound swept away microglia, the beta-amyloid remained, raising new questions about the part these plaques play in Alzheimer’s neurodegenerative process, researchers said. In healthy tissue, microglia act as the first and main form of immune defence in the central nervous system.
However, in a disease state, such as Alzheimer’s, microglia appear to turn against the healthy tissue they were originally assigned to protect, causing inflammation in the brain. The beta-amyloid plaques in brain areas related to Alzheimer’s disease are rich with these rogue microglia, researchers said.
“Our work is telling us that these cells may contribute to the disease process, and targeting them with such specific drugs is a promising new approach,” said Green. The findings were published in the journal Brain.