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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