Researchers at King’s College London have identified a potential new treatment for Alzheimer’s disease that targets DNA damage and brain inflammation. The experimental compound, known as KCL-286, demonstrated significant improvements in mouse models of the disease. This approach differs from many current therapies that focus primarily on removing toxic protein buildup in the brain.
KCL-286 Targets DNA and Inflammation
The study, published by King’s College London, highlights the drug’s ability to address multiple biological processes simultaneously. While much of the research into Alzheimer’s has concentrated on amyloid-beta and tau proteins, this new strategy targets earlier stages of cellular damage. KCL-286 was found to repair breaks in DNA strands and lower levels of inflammation in the brains of mice with Alzheimer’s-like conditions.
Professor Jonathan Corcoran, a professor of neuroscience at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, described the drug as a first-in-class, orally bioavailable small molecule. He noted that because KCL-286 has already completed Phase 1 human safety and tolerability trials, the timeline for further development could be significantly shortened. The drug is taken by mouth, which offers a more convenient administration method compared to injections or infusions used by some existing treatments.
The mechanism behind KCL-286 involves activating a protein in the retinoic acid pathway. This biological system is linked to how the body processes vitamin A, which plays roles in cellular development and nervous system function. Previous research had linked disruptions in this pathway to the formation of amyloid-beta deposits in rats, suggesting a connection to Alzheimer’s pathology.
From Spinal Cord Injury to Brain Disease
KCL-286 was originally developed to treat spinal cord injuries. Scientists at King’s College London discovered that acute spinal cord injury and Alzheimer’s disease share certain molecular pathways. This overlap led them to investigate whether a drug designed for nervous system damage after spinal trauma could also help with Alzheimer’s-related changes in neurons.
Earlier work showed that KCL-286 could promote the repair of DNA double-strand breaks in models of neuropathic pain. DNA double-strand breaks occur when both strands of the DNA molecule are severed, a serious form of damage that can disrupt cellular activity. Professor Corcoran compared these breaks to a rope snapping completely in two, rather than just fraying. The drug appears to help cells repair these breaks, allowing them to maintain normal function.
Dr. Maria Goncalves, who project-managed the drug development, stated that the findings demonstrate KCL-286’s potential as a disease-modifying therapy. She emphasized that the drug targets processes that occur very early in the disease progression, rather than just addressing symptoms. Natasha Hill, a first author on the paper, added that tackling multiple aspects of the disease is necessary for effective treatment.
The results suggest a shift in Alzheimer’s research toward addressing interconnected causes of brain damage. By targeting DNA damage and inflammation, KCL-286 offers a broader approach than focusing on a single hallmark of the disease. However, these findings remain preclinical. Additional studies and human clinical trials are required to determine if the drug can safely slow disease progression or improve outcomes in patients.
Source: ScienceDaily
