It almost doesn't hurt
The temporary shutdown of one gene saved the mice from severe pain
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A study conducted on mice showed that certain types of pain can be prevented without visible side effects by temporarily weakening the activity of a gene involved in the transmission of pain signals. If this approach withstands further trials, it may give patients with chronic pain a safer and longer-lasting treatment option compared to traditional opioid-based medications.
Despite the successes achieved in recent years by gene therapy in the fight against rare and life-threatening diseases, only a few scientists have tried to apply genetic approaches to the treatment of pain. This is partly due to the reluctance to permanently change the genome to eliminate sensations that are not always permanent or fatal. But the new approach does not imply changes in the DNA sequence and is theoretically reversible, so it can open up a new direction of research.
Nerve cells use protein channels in their membranes to transmit signals. One of these channels, known as Nav1.7, is associated with pain perception disorders. There are mutations that make the Nav1.7 protein overactive, and then carriers of these mutations are prone to attacks of acute pain. In other people, mutations of the corresponding gene deactivate Nav1.7, and these people do not feel pain at all. The Nav1.7 protein channel serves as an obvious target for pain medications, but blocking the channel proved difficult. Several of the first candidate drugs failed clinical trials. One of the main problems is the need to find a drug that binds to Nav1.7, but not to other proteins of the Nav family that are important for the functioning of the heart and other organs.
The authors of the new study decided not to disable Nav1.7, but to reduce the amount of this protein produced by cells. Two genome editing methods were used for this: CRISPR/Cas9 and "zinc fingers". In this case, the modified Cas9 protein binds to the desired DNA site, but does not cut it, but only prevents the synthesis of the Nav1 protein.7. The method was tested on mice treated with the chemotherapy drug paclitaxel, which can cause chronic nervous pain in cancer patients. Scientists confirmed their hypersensitivity to pain by touching the paws of mice with a thin nylon thread. The mice that received the drug pulled back their paws even with mild injections, that is, the stimulus that was usually painless for them became painful. But a month after injection into the cerebrospinal fluid, the mouse genome modification systems reacted the same way as the control group that had never received paclitaxel. The same mice whose Nav1.7 gene was not affected remained hypersensitive.
Scientists note that this method does not cause a complete loss of pain sensitivity. Behavioral tests have not yet revealed potentially dangerous side effects. Apparently, the injections did not affect the movements, cognitive abilities or anxiety level of the mice. It is unclear how long the pain reduction effect lasts, but during the study it persisted for ten months.
The results of the study are published in the journal Science Translational Medicine (Moreno et al., Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice).
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