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2027 Scholar-Innovator and ADDF-Harrington
Neuroscience
CK2 Inhibition as a Promising Target in Alzheimer's Disease
2025 Scholar, Harrington Brain Health Medicines Center
Several processes are known to contribute to the development and severity of Alzheimer’s disease. These processes, which include inflammation, abnormal metabolic activity and pathological cellular modifications, contribute to neuronal death, although they typically precede cognitive decline.
Dr. Gage and his team have found that the protein kinase CK2 activity is abnormally elevated in the brains of Alzheimer’s disease patients and in patient-derived models, making CK2 inhibition a promising therapeutic target. Protein kinases are enzymes that play a crucial role in regulating various cellular processes.
Dr. Gage notes that much Alzheimer’s research has focused on clearing beta-amyloid plaques in the brain, but he says that drugs targeting beta-amyloid have only been marginally effective in treating neurodegenerative disease in humans. He says his team’s purpose is to find new and better options for patients.
“There is a real search for new and different compounds that work through different mechanisms that might be more promising,” Dr. Gage says. “We’re part of the new vanguard of therapies that are targeting biological problems associated with the disease rather than targeting the pathology.”
With the support of Harrington Discovery Institute, Dr. Gage plans to accelerate his research into CK2 inhibitors. He and his team, Dr. Ioana da Silva and Dr. James Tucker, have generated more than 350 novel compounds, and their lead compound, TAL606, has shown tolerability and proof-of-concept efficacy in reducing neuroinflammation, boosting neurogenesis and rescuing dendritic loss in mice.
“CK2 inhibition shows promise for combating Alzheimer’s and other neurodegenerative diseases, and could be used with existing beta-amyloid therapies in a dual-targeted approach, and could be used either early or late in the course of therapy,” Dr. Gage says.
"Harrington's support is strong and ongoing; they make many good recommendations, and they're only a phone call away."