Gene therapy that inhibits targeted nerve cell signalling has effectively reduced neuropathic pain in trials, giving hope for a potential new treatment for a condition that can affect more than half of people living with spinal cord injury (SCI).
An international team of researchers found that the approach gave no detectable side effects in mice with spinal cord or peripheral nerve 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, the impact of which can have significant consequences mentally as well as physically.
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.
“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 Dr Martin Marsala, 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.”
Because clinicians and researchers are able to pinpoint the precise location of a spinal cord injury and origin of neuropathic pain, this has given rise to focus on developing 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, led by scientists at the University of California San Diego School of Medicine, 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.
