Pacifying pain: mouse study reveals a gene-therapy approach could be used to relieve chronic pain

Written by Heather Jones, Future Science Group

Researchers at Navega Therapeutics (CA, USA) have revealed that CRISPR, a gene-editing technique, could potentially be used to treat individuals with chronic pain. This follows a study applying the novel technique on mice administered with chemotherapy, known to commonly cause pain in cancer patients. Should the method be translated to humans and the treatment demonstrated to be safe, it could potentially provide an alternative to opioids. 

Physical pain is a problem we are all familiar with. Though it is generally manageable, it can be significantly debilitating for individuals with chronic, agonizing pain. Current medications have several drawbacks and despite decades of research, there has been little progress in the search for a broadly effective, long-lasting and non-addictive treatment for chronic pain, with a serious ongoing danger of opioid addiction for people with long-term pain conditions.

In this study, researchers used the genome-editing technology CRISPR on mice to silence SCN9A, a gene that codes for NaV1.7 channels, involved in the transmission of pain signals along the spinal cord. The methodology, termed ‘pain LATER’ (long-lasting analgesia via targeted in vivo epigenetic repression) uses an inactive Cas9 protein to silence SCN9A.

“You can either activate or repress a gene of interest, without creating permanent changes. So, we can repress the gene that’s known to cause sensitivity to pain,” explained Ana Moreno (Co-founder of Navega Therapeutics) to the Mail Online. “We are really excited because we have seen, in three different pain models, a decrease in overall pain.”

In order to treat the mice, the CRISPR editing tool was inserted inside inactive viral particles, which were then injected into the spine to infiltrate neuron cells.

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Mice were administered chemotherapy, which commonly results in pain for cancer patients. In order to manage pain from chemotherapy, patients are often given morphine, which can leave them feeling extremely fatigued. One of the benefits of this treatment as an alternative is that patients could potentially stay on chemotherapy for longer and live their lives more fully.

Further, the effects don’t wear off quickly, unlike conventional drugs. While acknowledging timeframes were not yet confirmed, Fernando Aleman (Navega Therapeutics) stated to the Mail Online that: “The effect may last ‘6 months to a year’ in humans.”

John Wood (University College London, UK) commented in the Mail Online that: “Most excitingly, the technology Navega has explored in animals can block chronic pain, without affecting the acute pain that is so useful in protecting us from burns and broken limbs through painful signals.”

This treatment has the potential to radically reform treatment for chronic pain, without the need for painkilling narcotics. However, Fyodor Urnov, a Professor at the University of California Berkeley (CA, USA), warns of a dark side to the treatment. Along with the currently unknown and unpredictable side effects, Urnov mentions how there may be the potential for misapplication of the technology for military purposes, such as producing a group of humans immune to pain.

Although gene therapy for pain has indicated promising results so far, human trials are yet to demonstrate success, with US researchers planning to start human trials next year.

Sources:; Guillen FA. Novel gene therapies for precision pain management. Pharmafile Autumn 2019 p18