Muscle spasms are a common and often debilitating consequence of spinal cord injuries and can have a significant impact on mobility and quality of life. Spasticity is a condition in which muscles become abnormally stiff or tense due to impaired nerve signal transmission, often causing hyperreflexia, involuntary muscle spasms, and difficulty moving. Current treatments can help manage symptoms, but often require continuous administration and can have side effects.
In a recent preclinical study, researchers evaluated a gene therapy approach designed to restore nerve signals that help keep muscle activity under control. This combination gene therapy targets the neurotransmitter gamma-aminobutyric acid (GABA) and the GABA-releasing mechanism (VGAT vesicular GABA transporter), which helps suppress neural activity. Previous studies have shown that spinal cord injury reduces GABA signaling, which may contribute to overactivity of neural circuits that cause muscle spasticity.
Using a rat model of chronic spinal cord injury-induced spasticity, the researchers used an inactivated virus to deliver therapeutic genes to spinal cord cells surrounding the injury site. This approach is designed to provide long-lasting results with a single treatment while targeting only the affected area of the spinal cord. Animals treated with this therapy showed a progressive reduction in spasticity, and significant improvements began to be observed after several weeks of treatment. The treatment also partially restored normal spinal reflex function and increased expression of therapeutic genes in spinal neurons involved in motor control.
The researchers also tested the safety of this therapy in several other animal models and found that the therapeutic vehicle remained confined to the targeted spinal cord region and caused no observable adverse effects on motor or sensory function for up to four and a half years. The findings suggest that a single dose of gene therapy targeting spinal cord segments may provide a long-term strategy to reduce muscle spasticity caused by spinal cord injury and other neurological conditions that may be associated with abnormal muscle tone.
sauce:
University of California, San Diego
Reference magazines:
Nguyen, D. others. (2026) Treatment of spinal cord injury muscle spasticity by subpial AAV9-GAD65/VGAT delivery: efficacy and safety studies in rats, pigs, and NHPs. molecular therapy. DOI: 10.1016/j.ymthe.2026.06.008. https://www.cell.com/molecular-therapy-family/molecular-therapy/abstract/S1525-0016(26)00485-5?_returnURL=
