MSGID: 1:317/3 6279eae5   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Gene therapy shows promise in treating neuropathy from spinal cord   
   injuries    
    In mouse studies, pain-blocking neurotransmitters produced long-lasting   
   benefit without detectable side effects    
      
     Date:   
         May 9, 2022   
     Source:   
         University of California - San Diego   
     Summary:   
         Researchers report that a gene therapy that inhibits targeted   
         nerve cell signaling effectively reduced neuropathic pain with   
         no detectable side effects in mice with spinal cord or peripheral   
         nerve injuries.   
      
      
      
   FULL STORY   
   ==========================================================================   
   An international team of researchers, led by scientists at University of   
   California San Diego School of Medicine, report that a gene therapy that   
   inhibits targeted nerve cell signaling effectively reduced neuropathic   
   pain with no detectable side effects in mice with spinal cord or   
   peripheral nerve injuries.   
      
      
   ==========================================================================   
   The findings, published in the May 5, 2022 online issue of Molecular   
   Therapy, represent a potential new treatment approach for a condition   
   that may affect more than half of patients who suffer spinal cord   
   injuries. Neuropathy involves damage or dysfunction in nerves elsewhere   
   in the body, typically resulting in chronic or debilitating numbness,   
   tingling, muscle weakness and pain.   
      
   There are no singularly effective remedies for neuropathy. Pharmaceutical   
   therapies, for example, often require complex, continuous delivery of   
   drugs and are associated with undesirable side effects, such as sedation   
   and motor weakness. Opioids can be effective, but can also lead to   
   increased tolerance and risk of misuse or abuse.   
      
   Because physicians and researchers are able to pinpoint the precise   
   location of a spinal cord injury and origin of neuropathic pain, there has   
   been much effort to develop treatments that selectively target impaired   
   or damaged neurons in the affected spinal segments.   
      
   In recent years, gene therapy has proven an increasingly attractive   
   possibility. In the latest study, researchers injected a harmless adeno-   
   associated virus carrying a pair of transgenes that encode for gamma-   
   aminobutyric acid or GABA into mice with sciatic nerve injuries and   
   consequential neuropathic pain. GABA is a neurotransmitter that blocks   
   impulses between nerve cells; in this case, pain signals.   
      
   The delivery and expression of the transgenes -- GAD65 and VGAT -- was   
   restricted to the area of sciatic nerve injury in the mice and, as a   
   result, there were no detectable side effects, such as motor weakness   
   or loss of normal sensation. The production of GABA by the transgenes   
   resulted in measurable inhibition of pain-signaling neurons in the mice,   
   which persisted for at least 2.5 months after treatment.   
      
   "One of the prerequisites of a clinically acceptable antinociceptive   
   (pain- blocking) therapy is minimal or no side effects like muscle   
   weakness, general sedation or development of tolerance for the treatment,"   
   said senior author Martin Marsala, MD, professor in the Department of   
   Anesthesiology in the UC San Diego School of Medicine.   
      
   "A single treatment invention that provides long-lasting therapeutic   
   effect is also highly desirable. These finding suggest a path forward   
   on both."  Co-authors include: Takahiro Tadokoro, UC San Diego,   
   University of Ryukyus, Japan and Neurgain Technologies, San Diego;   
   Mariana Bravo-Hernandez, Yoshiomi Kobayashi, Oleksandr Platoshyn,   
   Michael Navarro, Atsushi Miyanohara, Tetsuya Yoshizumi, Michiko Shigyo,   
   Rajiv Reddy and Joseph Ciacci, all at UC San Diego; Silvia Marsala,   
   UC San Diego and Neurgain Technologies, San Diego; Kirill Agashkov and   
   Volodymyr Krotov, both at Bogomoletz Institute of Physiology, Ukraine;   
   Stefan Juhas, Jana Juhasova, Duong Nguyen, Helena Kupcova Skalnikova and   
   Jan Motlik, all at Czech Academy of Sciences; Shawn P. Driscoll, Thomas D.   
      
   Glenn and Samuel L. Pfaff, all at Salk Institute for Biological Studies;   
   Taratorn Kemthong and Suchinda Malaivijitnond, both at Chulalongkorn   
   University, Thailand; Zoltan Tomori and Ivo Vanicky, both at Slovak   
   Academy of Sciences; Manabu Kakinohana. University of Ryukyus; and Pavel   
   Belan, Kyiv Academic University, Ukraine.   
      
      
   ==========================================================================   
   Story Source: Materials provided by   
   University_of_California_-_San_Diego. Original written by Scott   
   LaFee. Note: Content may be edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Takahiro Tadokoro, Mariana Bravo-Hernandez, Kirill Agashkov,   
      Yoshiomi   
         Kobayashi, Oleksandr Platoshyn, Michael Navarro, Silvia Marsala,   
         Atsushi Miyanohara, Tetsuya Yoshizumi, Michiko Shigyo, Volodymyr   
         Krotov, Stefan Juhas, Jana Juhasova, Duong Nguyen, Helena Kupcova   
         Skalnikova, Jan Motlik, Hana Studenovska, Vladimir Proks, Rajiv   
         Reddy, Shawn P. Driscoll, Thomas D. Glenn, Taratorn Kemthong,   
         Suchinda Malaivijitnond, Zoltan Tomori, Ivo Vanicky, Manabu   
         Kakinohana, Samuel L. Pfaff, Joseph Ciacci, Pavel Belan, Martin   
         Marsala. Precision spinal gene delivery-induced functional switch   
         in nociceptive neurons reverses neuropathic pain..   
      
         Molecular Therapy, 2022; DOI: 10.1016/j.ymthe.2022.04.023   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2022/05/220509150753.htm   
      
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