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2027 Scholar-Innovator and ADDF-Harrington
Neuroscience
Lead Optimization of SHIP1 Inhibitors and Biomarker Development for the Treatment of Alzheimer's Disease
2024 ADDF-Harrington Scholar
Today’s approved drugs for Alzheimer's disease (AD) can be traced to research on amyloid plaque—an abnormal level of a naturally occurring protein that forms plaques in the brain that are believed to cause neuronal disruptions. Although these medications help slow cognitive decline, their effectiveness is limited. With a novel approach, Dr. Richardson is targeting SHIP1, a protein involved in regulating microglia, the brain’s key immune cells.
SHIP1 is involved in neuroinflammation, which is associated with memory loss, confusion, and other AD symptoms. How the protein regulates microglia may be important in whether, and how fast, AD develops.
“Microglia are a double-edged sword,” Dr. Richardson says. “They can defend against or contribute to neurodegenerative processes. The SHIP1 protein plays an important regulatory role in the microglia. We believe it restrains microglial protective functions enabling processes that lead to neuroinflammation.”
“There are ‘super agers’ over 100 years old who have immune systems that are slightly more responsive than normal, yet the inflammation doesn’t cause AD,” he continues. “It’s the individuals whose microglia aren't dealing well with amyloid plaque who are more susceptible to AD.”
Dr. Richardson and his team have demonstrated success in inhibiting SHIP1, releasing microglial protective mechanisms to clear amyloid and other neurotoxins without causing harmful inflammation in mouse brains. With Harrington’s support, they aim to validate SHIP1 as a therapeutic target with a small molecule compound. With potential to advance to clinical trials and beyond, Dr. Richardson sees a future where AD is much better understood, preventable—and easily treated.
"Essentially, our approach is to encourage microglia to protect the brain. With early detection, a patient could take a medicine that maintains cognition for the rest of their life."