Current treatment is based on opioids, but these drugs can make people more sensitive to pain over time, leading to dependence on increasingly higher doses.
Gene therapy could avoid opioid use for chronic pain. The therapy, say researchers at the University of California, San Diego (USA), would be safer and less addictive than opioids, which have caused a veritable epidemic in countries like the USA.
As explained in ” Science Translational Medicine “, the new therapy works by temporarily suppressing a gene involved in pain detection. For now, the treatment improved pain tolerance in mice, reduced their sensitivity to pain, and provided months of relief without causing numbness.
The researchers say gene therapy could be used to treat a wide range of chronic pain, from low back pain to rare neuropathic pain disorders, situations for which opioid pain relievers are the current standard of treatment.
In Spain, it is estimated that 17% of the population lives with chronic pain
It is estimated that 1 in 5 people in the world experiences some type of chronic pain. According to the Spanish Pain Society (SED), in the US alone, 50 million people suffer from chronic pain on a daily basis, of which 19.6 million have high-impact chronic pain, that is, pain that frequently limits life or work activities. In Spain, it is estimated that 17% of the population lives with chronic pain.
Pain is seen as ‘ an unpleasant sensory and emotional experience with actual or potential tissue damage, or described in terms of such damage ‘. And chronic pain is the one that lasts for more than 3 months, or that lasts longer than the usual time expected for recovery. Monitoring pain that does not improve within 3 months is important as early pain management is the best way to prevent long-lasting and persistent chronic pain
“What we have now does not work,” says researcher Ana Moreno. Opioids can make people more sensitive to pain over time, leading to dependence on increasingly higher doses. “There is a desperate need for a treatment that is effective, long-lasting and non-addictive,” he says.
Researchers have worked on a genetic mutation that makes humans feel painless. This mutation inactivates a protein in neurons that transmit pain in the spinal cord, called NaV1.7. People who lack functional NaV1.7 do not register sensations such as touching something hot or stabbing like pain . And on the other hand, a genetic mutation that leads to NaV1.7 overexpression makes people feel more pain.
There is a desperate need for a treatment that is effective, long-lasting and non-addictive
This team had been working on gene repression using the CRISPR gene editing tool, specifically CRISPR which uses what is called ‘dead’ Cas9, which lacks the ability to cut DNA. Instead, if it attaches itself to a target gene, it blocks its expression.
This approach, Moreno points out, is attractive because “it does not remove any genes; that is, it does not produce permanent changes in the genome. The patient maintains his ability to feel pain.
The researchers engineered a killed CRISPR / Cas9 system to target and inactivate the gene encoding NaV1.7 and used their therapy in mice with chemotherapy-induced and inflammatory pain. The therapy achieved that these animals showed higher pain thresholds than those that did not receive gene therapy.
This approach is attractive because it does not remove any genes; that is, it does not produce permanent changes in the genome. The patient maintains his ability to feel pain
Furthermore, the treatment was still effective after 44 weeks in the animals with inflammatory pain and 15 weeks in those with chemotherapy-induced pain. Furthermore, the treated mice did not lose sensitivity or show any change in normal motor function.
To validate their results, the researchers ran the same tests using another gene-editing tool called zinc finger proteins. It is an older technique than CRISPR, but it does the same job . And spinal zinc finger injections in mice produced the same results as the CRISPR killed Cas9 system.
The researchers believe that this solution could work for a large number of chronic pain situations that arise from increased expression of NaV1.7
“Both approaches worked”, recognizes another of the scientists, Prashant Mali, who emphasizes that this second option is more translatable to the clinic because it is designed on the scaffold of a human protein.
The researchers believe this solution could work for a host of chronic pain situations arising from increased NaV1.7 expression, including diabetic polyneuropathy, erythromelalgia, sciatica, and osteoarthritis. It could also bring relief to patients undergoing chemotherapy.
And because of its non-permanent effects, it could address an unmet need of a large population of patients with long-lasting (weeks to months) but reversible pain conditions.
