Experimental cancer drug offers clues to new kind of pain therapy
New research published in the journal Nature Communications has identified a potential treatment for chronic pain in an old experimental cancer drug. The research homed in on the drug by screening over a thousand different molecules in the search for one that can enhance the expression of a gene implicated in chronic pain.
“Because chronic pain, like many chronic diseases, has an important root in genetic switches being reprogrammed in a bad way, a disease modifying treatment for chronic pain should reset the genetic switches, not just cover up the pain, as with opioid and aspirin/Tylenol-like painkillers,” explains Wolfgang Liedtke, one of the researchers working on the project.
The research focused on a gene called KCC2, which encodes a molecule known to help expel chloride ions from neurons. Low chloride levels in neurons can inhibit pain signaling and research has demonstrated reduced KCC2 expression in many forms of chronic pain.
So the researchers set out to investigate whether any previously developed drugs could enhance KCC2 expression. Because many cancer drugs influence gene expression the study began by surveying more than 1,000 pre-existing molecules from a “junkyard of cancer drugs” – experimental compounds that were mostly abandoned at different stages of research.
The research ultimately homed in on a drug called Kenpaullone, a molecule first investigated decades ago as a cancer treatment before being abandoned during preclinical research stages. Drugs with similar actions to kenpaullone are currently being trialed for Alzheimer’s disease and muscular dystrophy.
Across a series of impressive preclinical experiments the new study demonstrated kenpaullone effectively reducing signs of pain in several animal models. As well as demonstrating this drug can relieve pain, the researchers described the likely analgesic mechanism by which kenpaullone works.
The main outcome from the research is less about demonstrating kenpaullone to be a specific future pain-relieving drug and more about discovering a new way to treat chronic pain. Kenpaullone is a type of drug known as a GSK-3 inhibitor.
Tideglusib, another GSK-3 inhibitor, has recently demonstrated positive safety data in early human trials. Liedtke and colleagues speculate this drug could be repurposed as an analgesic either after it is approved for other uses or sooner if clinical trials specifically focusing on pain can be arranged.
“Ongoing clinical development of GSK3ß-inhibitory tideglusib, which is in phase-II trials for congenital myotonic dystrophy, could conceivably lead to its repurposing for pain, following approval for its primary, proposed indication,” the new study concludes. “Even if not imminent anytime soon, since safety data appear to be re-assuring, a clinical trial for pathologic pain with tideglusib as a clinically well-developed GSK3ß inhibitor can now be envisioned.”
The new study was published in the journal Nature Communications.