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Gene therapy effectively reduces neuropathic pain in mice with spinal cord injury

Gene therapy effectively reduces neuropathic pain in mice with spinal cord injury

 


An international research team led by scientists at the University of California, San Diego Medical School, found that genetic therapy that inhibits signaling in target neurons causes neuropathic pain in mice with spinal or peripheral nerve damage without detectable side effects. It reports that it was effectively reduced.

Survey results published online on May 5, 2022 Molecular therapyRepresents a potential new therapeutic approach to conditions that can affect more than half of patients suffering from spinal cord injury. Neuropathy is associated with nerve damage or dysfunction elsewhere in the body, usually resulting in chronic or debilitating numbness, tingling, weakness and pain.

There is no very effective treatment for neuropathy. For example, drug therapy often requires complex and continuous delivery of the drug, with unwanted side effects such as sedation and weakness in exercise. Opioids are effective, but they can also lead to increased tolerance and the risk of misuse and abuse.

Physicians and researchers can identify the exact location of spinal cord injury and the cause of neuropathic pain, so much to develop treatments that selectively target disorders or damaged neurons in the affected spinal cord segment. Efforts have been made.

In recent years, gene therapy has proved to be an increasingly attractive potential. In the latest study, researchers injected mice with sciatic nerve injury and consequent neuropathic pain with a harmless adeno-associated virus carrying a pair of transgenes encoding gamma-aminobutyric acid or GABA. GABA is a neurotransmitter that blocks impulses between nerve cells. In this case, it is a sign of pain.

Transgene delivery and expression-; GAD65 and VGAT-; Confined to the area of ​​sciatic nerve injury in mice, resulting in no detectable side effects such as impaired movement or loss of normal sensation. The production of GABA by the transgene resulted in measurable inhibition of pain signaling neurons in mice, which persisted for at least 2.5 months after treatment.

One of the prerequisites for clinically acceptable anti-nociceptive (pain blockade) therapy is minimal or no side effects such as weakness, general sedation, or development of tolerance to treatment. is. A single therapeutic invention that provides a long-term therapeutic effect is also highly desirable. These findings suggest a path to both progress. “


Martin Marsala, MD, Senior author, Professor, Department of Anesthesiology, University of California, San Diego School of Medicine

Source:

Journal reference:

Toru Tadokoro, et al. (2022) Precise spinal gene delivery-inducing function switches in nociceptive neurons reverse neuropathic pain. Molecular therapy.. doi.org/10.1016/j.ymthe.2022.04.023..

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