Posted on 30 March 2021
Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.
Why is this research important: Many adults suffer from some form of chronic pain (around one in 5 adults in the US, according to the CDC). Opioids are widely used in the Unitied States as a treatment for chronic pain, but can result severe side effects, addiction, and tolerance (they become less effective over time). In order to transmit electrical signals, nerves including those that sense pain rely on the passage of ions through protein channels in their membranes. One such channel that appears to be particularly important in pain signals is Nav1.7. Those with rare mutations that deactivate Nav1.7 are insensitive to pain but experience no other neurological effects, making it an enticing drug target. However, this channel bears close resemblance to other ion channels, making it difficult to develop drugs that deactivate Nav1.7 and only Nav1.7.
What did the researchers do: In this study, researchers used two gene editing technologies – CRISPR-Cas9 and zinc fingers – to target the Nav1.7 gene. The technology was modified to suppress the DNA coding for Nav1.7, rather than deleting it entirely, and was loaded into an adeno-associated virus. The treatment was then injected into the spinal fluid in three mouse models of chronic pain.
Key takeaway(s) from this research: While untreated mice experienced pain in response to normally non-painful stimuli (such as having their paws gently poked), treated mice did not. The mice didn’t appear to suffer any negative side effects, and still responded normally to stimuli in areas not affected by chronic pain, suggesting that the treatment did not produce a level of numbing that would be dangerous.
We don’t know how long these effects last, but it is at least 10 months according to this study. Because the treatment doesn’t make any permanent changes to the DNA, it is expected that the effects would naturally diminish over time. Researchers are now preparing to test this treatment in nonhuman primates – the next step towards seeing it used in humans.
Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice: DOI: 10.1126/scitranslmed.aay9056
Gene-silencing injection reverses pain in mice: https://www.sciencemag.org/news/2021/03/gene-silencing-injection-reverses-pain-mice