Gene therapy could ease chronic pain by simulating the pain-killing properties of opiate drugs, researchers from the Departments of Medicine and Neurosciences at Mount Sinai School of Medicine have found, reporting in the Proceedings of the National Academy of Sciences.
The research team designed a cold virus to carry the prepro-b-endorphin gene, which makes an opioid that the body produces naturally, into primary sensory neurons in order to activate opiate receptors, thereby mimicking morphine-like painkillers. The procedure was tested in rats that had been engineered to experience chronic pain, with the virus being delivered via lumbar puncture. The researchers found that the rats remained symptom-free for three months. Professor Andreas Beutler, principle scientist on the study, stated 'opioids are unequivocally effective in humans, for example, morphine and oxycodone are among the most active analgesics. Thus it is highly unlikely that the opioid-gene based approach in our paper would be limited to rodents'.
As many as 50 million Americans and 21 per cent of Europeans suffer from long-term chronic pain. The British Pain Society has estimated that back pain costs the UK £5 billion per annum. Pain relieving treatments that are currently available are either ineffective or have intolerable side effects, and also carry the risk of addiction when used over long periods of time. Studies have also suggested that the drugs available do not relieve cancer pain in as many as 66 per cent of patients. Gene therapy could potentially have fewer side effects than existing pain medications, because it travels directly along the spinal chord, sparing the brain and other organs from its effects.
The team found that another pain-relief gene, interleukin-10, was also effective, raising the possibility of a non-opioid approach to pain relief. However, Professor Beutler warned that it was not clear whether interleukin-10 would be effective in humans, and highlighted problems with the testing procedure, 'because it would be very difficult to infuse interleukin-10 for a prolonged period of time at the spinal level because of the risks associated with long-term spinal catheters'.
Professor Beutler stated that gene therapy via lumbar puncture was the most promising new development for those who suffer from long-term chronic pain, and estimated that the first clinical trial in humans could take place within three to five years. Josephine Querido, of Cancer Research UK, said 'although this research is at a very early stage, the concept of using gene therapy to deliver pain relief is interesting, because it could potentially have fewer side effects than conventional pain relief'.
The findings come only days after Professor Hanns Ulrich Zeilhofer and his team at the University of Zurich found a pain relief target in the spine, which sends signals from pain nerves to the brain. Professor Beutler commented, 'their work contributes very substantially to our understanding of pain mechanisms'.
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