A drug developed 20 years ago to treat cancer may help patients suffering from severe pain, according to new research.
Scientists say Kenpaullon switches on a gene that reduces chronic inflammation.
Experiments on rats and humans found that it was remarkably successful in reducing symptoms of nerve injury and bone tumors.
The US team hopes that clinical trials in humans suffering from several conditions will see equally successful results.
8 million people in the UK live with chronic pain. Major causes include arthritis and damage to the spine.
Lead author Professor Wolfgang Lidtke said: “New drugs and other treatments against chronic pain need to be safe, that is, the fewer side effects the better.
“It is particularly important that they be non-addictive and non-sedative, while being effective against nerve injury pain and cancer pain, as well as with the shortest time for official approval.
“Since chronic pain, like many chronic diseases, has an important root in poorly reprogrammed genetic switches, a disease modifying treatment for chronic pain must reset the genetic switch, not just cover up the pain. As should opioids and pain-relieving drugs like aspirin/Tylenol.”
Professor Lidtke practiced pain medicine at Duke University in North Carolina for the past 17 years and is now an executive at Regeneron Pharmaceuticals in New York.
Globally, approximately 1.5 billion people suffer from chronic pain. It affects an estimated 50 million in the US.
One bone cancer patient said: “I can’t sleep anymore because turning over in bed hurts, my spine hurts, and sitting down to sleep hurts even more.
“During the day, I have persistent brain fog, interrupted by pain that within minutes gets worse 10 out of 10, against a background of constant burning pain that worsens towards noon and evening.
“I have more pain when I go to the bathroom. Pain medication makes my brain fog worse. I feel like a zombie. I’m terribly constipated and itchy all over. “
Similarly, people with chronic nerve damage due to diabetes, medication side effects or severe shingles describe their lives as suffering.
Prof. Lidtke and his colleagues surveyed the “junk of cancer drugs” seeking better treatments that have potential for repurchase.
They tested more than 1,000 compounds contained in two libraries at the National Cancer Institute.
In addition to preventing cells from multiplying, many reset the maladaptive genetic switch in non-dividing nerve cells.
In mice with bone cancer, kenpaulone was found to inhibit pain caused by nerve constriction.
This triggered a gene called Kcc2, which removes chloride from neurons. Silent signals between low level cells – alleviating pain.
In all types of chronic pain studied in experimental animals and human spinal cord models, Kcc2 disappeared from neurons forming the primary pain gate.
Prof Lidtke said: “Kenapolone is an effective analgesic for chronic and challenging-to-treat pain, such as those caused by nerve injury and bone cancer. It reprograms pathways.
“Pain relief was intense, long-lasting and with a prolonged onset, consistent with the drug’s effect on gene regulation.
“At this stage, we knew that we met the basic requirement of our screen of KCC2 gene expression-enhancer-identified cancer drugs, and demonstrated that they could be used as an analgesic in valid pre-clinical pain models. Huh.”
Further tests yielded “great positive results”. They showed that kenepolone affects the spinal cord’s processing of pain.
It also reduces the elevation of nerve injury-induced chloride levels in pain-relieving neurons.
Researchers discovered the underlying mechanism. Kenpaullon blocks a pain-relieving enzyme called GSK3-beta that turns off a gene called delta-CAT.
Prof Lidtke said: “These findings suggest that delta-CAT gene therapy, along with kenapolone and similarly-acting kinase-inhibitory compounds, has the potential to become new tools in our toolbox against chronic refractory pain, Including nerve injury pain and canker bone pain, and likely against other forms of chronic pain associated with reduced Kcc2 expression.
“This approach may also be effective against other neurologic and psychiatric disorders in which this mechanism contributes to disease.”
The study, published in the journal Nature Communications, identified three other highly promising drugs that may do the same thing.
Credit: www.independent.co.uk /