Researchers into Alzheimer‘s seemed to keep coming back to the same two suspects for decades: amyloid-beta and tau. Scientists knew these proteins were there, building up in brains of sick people and doing terrible things. So they went after them. A lot of money was spent on drugs that were supposed to get rid of amyloid. Some of them worked a little. Saddened the most. Something was missing from the field, and it was always there, but not loud. There’s a chance that something was always hidden in the DNA.
King’s College London researchers recently shared their findings on a drug called KCL-286. This drug was first created to treat spinal cord injuries, not Alzheimer’s. It’s amazing how much it can change a mouse model of Alzheimer’s disease. Instead of focusing on just one part of the disease, KCL-286 seems to fix DNA double-strand breaks and lower brain inflammation at the same time. These are two things that happen in the very early stages of the disease, before the well-known protein buildups happen.
“DNA double-strand breaks” is an easy phrase to skip over. The Professor of Neuroscience at King’s College London’s Institute of Psychiatry, Psychology, and Neuroscience, Jonathan Corcoran, gave a more human way to think about it: he said it’s like a rope snapping in half instead of fraying at the edges. If you don’t fix that kind of damage, it builds up. A lot of it builds up in the brains of people with Alzheimer’s. KCL-286 seems to help fix these breaks, which is what makes this approach feel truly different, both in terms of scope and timing—it’s going after something upstream.
The retinoic acid pathway is the body’s way of processing vitamin A, and KCL-286 works by turning on a certain protein in it. Previous studies had already shown that problems in this pathway were linked to the buildup of amyloid-beta in rat brains. And studies on neuropathic pain had already shown that the drug might be able to fix DNA damage. The jump to Alzheimer’s wasn’t random; it was made along a thread.
The history of the drug changes the way this research is done. KCL-286 has already passed Phase 1 tests to make sure it is safe and well tolerated by humans. That is very important. It usually takes years and a lot of money to get a new molecule from the idea stage to the point where it is safe to give to a person. As Professor Corcoran pointed out, this will cut the time it takes to make a new drug by a huge amount compared to the past. It’s still not clear when or how quickly it could move into human trials for Alzheimer’s, but the time frame is shorter than for a drug that starts from scratch.
Dr. Maria Goncalves, who oversaw the development of the drug, said that the results pointed to a more meaningful treatment than just managing symptoms: a disease-modifying therapy that could change how the condition gets worse instead of just making its symptoms less severe. That difference is important to people who have been sick and their families who have seen the disease progress slowly but steadily.
It’s hard to put a number on it, but this research gives me the impression that Alzheimer’s research is slowly becoming more comprehensive. It was never completely wrong to only look at amyloid—it’s there and it’s bad—but it was also missing some information. These aren’t small side stories: inflammation, DNA damage, and the body’s own repair systems not working right. They might be early stages of Alzheimer’s disease. If you go after them, you might catch the disease before it writes the rest of the story. Even though KCL-286 is still early in its Alzheimer’s journey, it shows that possibility is at least worth thinking about.
