In rat studies, blocking pain neurotransmitters produced long-term benefits without detectable side effects.
An international team of researchers led by scientists at the University of California San Diego School of Medicine reports that a gene therapy that blocks targeted neuron signaling effectively reduces neuropathic pain in mice with spinal cord injuries or peripheral nerve injuries without any detectable side effects.
The results have been published in the online version of Molecular Therapy On May 5, 2022, he proposed a potential new treatment option for a condition that may affect more than half of individuals with spinal cord injuries. Neuropathy involves damage or dysfunction of nerves elsewhere in the body, usually resulting in chronic or debilitating numbness, tingling, muscle weakness, and pain.
There are no single effective treatments for neuropathy. Pharmacotherapy, for example, may require advanced and continuous pharmacological management and is associated with adverse side effects such as drowsiness and motor impairment. Opioids may be effective, but they can also develop tolerance and increase the risk of overuse or addiction.
As clinicians and researchers are able to pinpoint the exact location of a spinal cord injury and the origin of nerve pain, there have been many efforts to develop treatments that selectively target weak or damaged neurons in the affected segments of the spine.
In recent years, gene therapy has proven an increasingly attractive possibility. In the latest study, researchers injected a harmless gland-associated virus carrying a pair of transgenes that code for gamma-aminobutyric acid, or GABA, into mice with sciatic nerve injuries and subsequent neuropathic pain. GABA is a neurotransmitter that blocks impulses between nerve cells. In this case, pain signals.
Transgene delivery and expression – GAD65 and VGAT – were restricted to the sciatic nerve injury area in mice, and as a result, there were no detectable side effects, such as motor impairment or loss of normal sensation. Production of GABA by the transgene resulted in a measurable inhibition of pain signaling neurons in mice, which persisted for at least 2.5 months after treatment.
Said senior author Martin Marsala, MD, professor in the department of anesthesiology at the University of California, San Diego School of Medicine.
“Inventing a single treatment that provides a long-lasting therapeutic effect is also highly desirable. These results suggest a path forward for both.”
Reference: “Spinal gene delivery-induced subtle functional switching in nociceptive neurons mirrors neuropathic pain” by Takahiro Tadokoro, Mariana Bravo-Hernandez, Kirill Agashkov, Yoshimi Kobayashi, Alexander Platochin, Michael Navarro, Sylvia Marsala, Atsushi Miyanoigumi and Tates , Volodymyr Krutov, Stefan Johas, Jana Guhsova, Duong Nguyen, Helena Kupkova Skalnikova, Jan Motlik, Hana Stodinowska, Vladimir Brooks, Rajiv Reddy, Sean B. Driscoll, Thomas D. , Manabu Kakinohana, Samuel Pfaff, Joseph Siachi, Pavel Bilan and Martin Marsala, May 5, 2022, Molecular therapy.
DOI: 10.1016 / j.ymthe.2022.04.023