June 09, 2026 —
Researchers at UC San Diego School of Medicine have reported preclinical findings supporting a gene therapy approach to reduce muscle spasticity after spinal cord injury. The study, led by Martin Marsala, MD, professor of anesthesiology at UC San Diego, was published in Molecular Therapy.
Muscle spasticity is a common and often debilitating consequence of spinal cord injury. It occurs when disrupted nerve signaling causes muscles to become abnormally stiff or tight, leading to exaggerated reflexes, involuntary spasms, and difficulty with movement. Current treatments can help manage symptoms, but they often require repeated administration and may be associated with systemic side effects.
The new study evaluated a spinal segment-targeted gene therapy designed to restore inhibitory signaling in the spinal cord. The approach targets gamma-aminobutyric acid, or GABA, a key inhibitory neurotransmitter, together with VGAT, the vesicular GABA transporter involved in GABA release. Previous research has shown that spinal cord injury can reduce GABA signaling, contributing to overactive neural circuits that drive spasticity.
Using a rat model of chronic spinal cord injury-induced spasticity, researchers delivered therapeutic genes to spinal cord cells near the injury site using an inactive viral vector. The goal was to provide a long-lasting therapeutic effect from a single administration while limiting activity to the affected spinal cord region.
Animals treated with the gene therapy showed a progressive reduction in spasticity, with significant improvements beginning several weeks after treatment. The therapy also partially restored normal spinal reflex function and increased expression of the therapeutic genes in spinal neurons involved in motor control.
The research team also evaluated safety in several animal models. The treatment vehicles remained confined to the targeted spinal cord region, and no observable negative effects on motor or sensory function were reported for up to 4.5 years.
Although the findings remain preclinical, the study suggests that a single administration of spinal segment-targeted gene therapy may provide a durable strategy for reducing muscle spasticity caused by spinal cord injury. If further validated, this approach could also have potential relevance for other neurological conditions involving abnormal muscle tone and disrupted inhibitory signaling.
