Accumulation of DNA damage in the brain’s neurons may contribute to the development of Alzheimer’s disease. New research in FEBS Open Bio demonstrates the therapeutic potential of a drug that targets this process.
Using a mouse model of Alzheimer’s disease, investigators found that treatment with KCL-286, a molecule that activates the retinoic acid receptor-β (RARβ), enhanced the repair of DNA damage in neurons. Activation of the receptor triggers a pathway that ultimately causes a protein complex to bind to DNA and promote the expression of certain repair genes. KCL-286 also reduced neuronal inflammation and abnormal brain immune activity, processes thought to contribute to Alzheimer’s disease development and progression.
“We think of the drug as repairing potholes in a road—once the damage is fixed, normal traffic can flow again and the system settles down. By repairing the underlying damage, we can allow the system to reset,” said corresponding author Jonathan Corcoran, PhD, Professor of Neuroscience at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London. “This principle may extend beyond Alzheimer’s to nerve repair and neurodegeneration more broadly.”
Prof. Corcoran noted that phase I clinical trials have already established a favorable safety profile for KCL‑286 in humans. With appropriate funding, investigators can next test whether this approach delivers meaningful benefit to patients. "The opportunity is immediate, and the science is ready to advance," he said.
URL: https://onlinelibrary.wiley.com/doi/10.1002/2211-5463.70284
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FEBS Open Bio is an open access journal for the rapid publication of research articles across the molecular and cellular life sciences. The journal’s rigorous peer review process focusses on the technical and ethical quality of papers, rather than subjective judgements of significance.
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