Gene Therapy Approach Reduces Muscle Spasticity After Chronic Spinal Cord Injury

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Muscle spasticity is a common and often debilitating consequence of spinal cord injury that can significantly affect mobility and quality of life. Spasticity is a condition in which muscles become abnormally stiff or tight because of disrupted nerve signaling, often causing exaggerated reflexes, involuntary muscle spasms and difficulty with movement. Current treatments can help manage symptoms, but they often require ongoing administration and may be associated with side effects.

In a recent preclinical study, researchers evaluated a gene therapy approach designed to restore the nerve signals that help keep muscle activity under control. The combined gene therapy targets gamma-aminobutyric acid (GABA), a neurotransmitter and GABA-releasing machinery (VGAT-vesicular GABA transporter) that helps dampen nerve activity. Previous research has shown that spinal cord injury can reduce GABA signaling, contributing to the overactive nerve circuits that drive muscle spasticity.

Using a rat model of chronic spinal cord injury-induced spasticity, researchers used an inactive virus  to carry the therapeutic genes into spinal cord cells around the injury site. The approach is designed to provide a long-lasting effect from a single treatment while targeting only the affected region of the spinal cord. Animals treated with the therapy showed a progressive reduction in spasticity, with significant improvements observed beginning several weeks after treatment. The therapy also partially restored normal spinal reflex function and increased expression of the therapeutic genes within spinal neurons involved in motor control.

The researchers also tested the treatment for safety in several other animal models, finding that the treatment vehicles remained confined to the targeted spinal cord region and caused no observable negative effects on motor or sensory function for up to 4.5 years. The findings suggest that a single administration of spinal segment-targeted gene therapy may provide a long-lasting strategy for reducing muscle spasticity caused by spinal cord injury and potentially other neurological conditions associated with abnormal muscle tone.

The study, "Treatment of spinal injury muscle spasticity by spinal subpial AAV9-GAD65/VGAT delivery: an efficacy and safety study in rat, pig and NHP", led by Martin Marsala, MD, professor of anesthesiology at UC San Diego School of Medicine, published on June 4, 2026 in Molecular Therapy.