Pain Relief? It's In Your Genes...
CRISPR Treatment for Chronic Pain
*ARTICLE UPDATE: The FDA approved the first CRISPR-based treatment for Sickle Cell Disease on Dec. 8, 2023.
For a full overview of CRISPR-CAS9 and how it works, see my article here.
A new method of treating chronic pain may be on the horizon with the help of the gene editing technology, CRISPR-CAS9. While most chronic pain in humans is treated using narcotic drugs, including opiates, new research presents an alternative solution to pain treatment that is more effective long term and has a lower risk of addiction, a common side effect of opiate use.
Pain is an important thing to experience. From a young age, pain is how we learn how to actively prevent damage to our bodies, what to pay attention to, and what to avoid to ensure the best possible chance of our survival. However, in the case of chronic pain, the feeling serves less as a warning than as a foregone conclusion. For some, it can become a constant ongoing struggle to living a normal life.
Until now, prescription painkillers, including opiates such as Oxycodone, have been the main solution. However, painkillers such as these can be highly addictive. As the body builds up a tolerance to the drug, more and more is needed for the same result. The body also slows down production of its own natural painkillers, so when the patient stops taking the drug, they are hit with an even higher sensitivity to pain than before. Opiates prescribed for pain can also serve as gateway drugs. Their addictive properties lead to the risk of patients self-medicating with other drugs once their prescription runs out, which can be dangerous.
What if we were able to prevent pain not by masking it, but by blocking the perception of pain you experience?
Pain and the Brain:
Pain is transmitted through the nervous system through the pumping of ions, or small, charged atoms, through your neural networks. This generates an electrical current that is transmitted to the brain and interpreted as ‘pain’. This pumping of ions in situations associated with pain is controlled by the expression of the gene nicknamed Nav1.7.
DNA is ‘read’ by being fed through a protein called RNA Polymerase. As the RNA Polymerase slides down the DNA strand, it spits out a molecule called messenger RNA (mRNA). mRNA is the shorthand for the DNA code that then can be used to ‘tell’ your cells what to do.
If you can block the RNA Polymerase from reading a gene in your DNA, mRNA won’t be produced, and the process stops there. We can block RNA Polymerase by physically covering up that piece of DNA, usually with a protein called an inhibitor. Your body blocks genes all the time using this strategy. It’s the reason the genes for growing hair are only expressed in your skin cells, and not in say, your tongue cells, or your heart cells.
Normally, NaV1.7 is triggered when a nerve cell comes into contact with a painful stimulus. The inhibitor protein covering up NaV1.7 detaches, and the RNA Polymerase’s path is no longer blocked. It reads the NaV1.7 gene, and mRNA delivers instructions for the cell to start pumping ions to the brain. When the stimulus goes away, the protein moves back into place, and the ions stop being produced.
In the case of chronic pain, the trigger for nerve cells is constantly being switched on. NaV1.7 is working overtime to alert the brain that there is a source of pain nearby.
Using lessons from CRISPR-CAS-9, scientists modified a CAS-9 protein by adding zinc to make it ‘stick to’ the NaV1.7 gene, closing up that pathway with RNA Polymerase. This is called repressing a gene. With NaV1.7 out of commission, the cells are no longer receiving instructions to express the pain.
And Voila! A completely drug-free painkiller that tricks the body’s own system into thinking the pain has gone away. Â
The new painkiller was nicknamed LATER, an acronym for Long-Lasting Analgesia via Targeted Epigenetic Repression. It’s still in the testing stages, but so far has shown a lot of promise.
The mice utilized in this study were exposed to various chronic pain-causing stimuli, including chemotherapy and inflammatory drugs. The mice who were treated with the CAS-9 NaV1.7 inhibitor had a significant drop in sensitivity to pain for both types of stimuli.
Interestingly enough, the mice with the CAS-9 treatment were also less sensitive to heat and cold stimuli. This is likely because heat and cold are registered by the body using similar ion-pumping pathways.
Note that ion pumping in the nervous system produces other sensations including smell, anxiety, social behaviors, and memory. Various tests were performed on the mice, and it was found that the inhibition of the NaV1.7 gene did not have an effect on any of the other sensations listed above.
What with CRISPR research being a vastly growing field, and the FDA expected to approve the first CRISPR-based treatment this December*, it’s possible that a CRISPR-CAS9 pain inhibitor on the market will greatly decrease the use of opioids and narcotics for pain treatment. Opiates are highly addictive substances, and using a CAS9 pain inhibitor like LATER would be a desirable alternative to eliminate risks of chronic dependence on these painkillers for relief, as well as risks of opioid overdoses.
However, blocking pain receptors may come with its own consequences, most notably that patients may lose vital warnings of strain on the body. Pain receptors are a safeguard to prevent activities that can damage the body. Chronic pain from areas such as the back or knees is a message that these areas have experienced severe strain in the past, and that they should not be over-exerted. A person who can no-longer feel their chronic pain may forget or be unaware of this fragility, and may engage in activities that exacerbate the existing problems and could lead to further damage. While it may not be suitable for every case, one thing’s clear:
LATER may be sooner than you think.
Read the full study:
Moreno, A. M., Alemán, F., Catroli, G. F., Hunt, M., Hu, M., Dailamy, A., … Mali, P. (2021). Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice. Science Translational Medicine, 13(584). https://doi.org/10.1126/scitranslmed.aay9056
Read about the first CRISPR-based Treatment approved by the FDA:
https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease
I’m surprised that you see nothing wrong with altering our dna. That’s mind boggling