Scientists at King’s College London report that an experimental compound, KCL-286, repaired markers of DNA damage and lowered brain inflammation in a mouse model of Alzheimer’s disease. The team says the drug—originally developed for spinal cord injury—has already completed Phase 1 safety and tolerability testing in humans, which could speed plans for further clinical studies.
Researchers at King’s College London say they have identified a potential new approach to Alzheimer’s treatment that targets biological changes thought to appear early in the disease course.
In work published in FEBS Open Bio, the team reports that KCL-286—described as a “first-in-class” retinoic acid receptor beta (RARβ) agonist—reduced signs of neuronal DNA damage and lowered inflammation in the brains of mice used as a model of Alzheimer’s disease.
Professor Jonathan Corcoran, a neuroscientist at King’s College London who led the research, said the compound is an orally bioavailable small molecule and has already “cleared Phase 1 human safety and tolerability trials,” a milestone he said could shorten typical development timelines.
Dr Maria B. Goncalves, who project managed the drug development, said the findings suggest KCL-286 may have potential as a disease-modifying therapy because it affects both DNA damage and inflammation—processes the researchers describe as occurring very early in Alzheimer’s progression.
Natasha Hill, one of the paper’s first authors, said the study supports a strategy of aiming at multiple disease-relevant pathways rather than a single hallmark.
According to King’s, the drug acts within the retinoic acid pathway involved in vitamin A biology, and the researchers pointed to prior work linking disruptions in this pathway to Alzheimer’s-related changes. They also said earlier evidence that KCL-286 can promote repair of DNA double-strand breaks in other neurological contexts helped motivate testing the compound in an Alzheimer’s mouse model.
The researchers emphasized that the evidence reported so far comes from mouse studies, and further work would be needed to determine whether the approach translates to people with Alzheimer’s disease.
The study was funded by the UK Medical Research Council and the Wellcome Trust, King’s said.
