A groundbreaking study by researchers at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), has revealed that a class of cancer drugs, histone deacetylase inhibitors (HDACi), can significantly reduce brain damage and promote recovery after stroke. Published in the journal GLIA, the findings offer hope for new treatment strategies that address the secondary inflammation following stroke, a leading cause of disability and death worldwide.
The study demonstrated that HDACi drugs, already used or tested for cancer and neurodegenerative diseases like Alzheimer’s, can reprogram microglia—the brain’s immune cells—from an inflammatory state to a protective one. In laboratory models simulating stroke, HDACi treatment reduced brain damage by 60% and improved behavioral outcomes. Advanced techniques like spatial transcriptomics revealed how these drugs restore neuroprotective gene activity in specific brain regions, including the hippocampus, which is critical for memory.
Current stroke therapies focus primarily on restoring blood flow and are time-sensitive. This research opens the door to treatments that target the harmful inflammation occurring days after a stroke, potentially extending the therapeutic window. Professor S Thameem Dheen, the lead author, emphasized the clinical potential: “HDACi can dampen brain inflammation and promote recovery through a microglia-centric mechanism.”
The team aims to develop therapies that act beyond the acute phase of stroke, repairing brain circuitry and preserving function. Co-author Dr. Kevin Jayaraj highlighted the broader implications: “Our findings represent an out-of-the-box approach for conditions where neuroinflammation plays a key role.”
This study marks a significant step toward innovative stroke treatments, offering new hope for patients and clinicians alike.
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