Researchers at UC San Diego have developed a one-time gene therapy treatment that could transform how doctors address muscle spasticity, one of the most debilitating consequences of spinal cord injury. Led by Martin Marsala, MD, professor of anesthesiology at UC San Diego School of Medicine, the team's preclinical study published in Molecular Therapy shows that a single injection can trigger progressive improvements in muscle stiffness and control that last for years.
Spasticity—the abnormal muscle rigidity, involuntary spasms, and exaggerated reflexes that follow spinal cord injury—affects mobility and quality of life for countless patients. Current treatments manage symptoms but require ongoing doses and often come with unwanted side effects. This breakthrough targets the root cause: a breakdown in the nerve signals that normally keep muscles relaxed and responsive.
The therapy works by restoring GABA signaling, a crucial neurotransmitter system that dampens nerve activity. When the spinal cord is injured, GABA levels drop, allowing overactive nerve circuits to drive the muscle stiffness. Marsala's team designed a treatment that delivers two therapeutic genes—one for GABA production and one for the machinery that packages and releases it—directly to spinal cord cells around the injury site. They used an inactive virus as a molecular delivery vehicle, a proven strategy that allows the genes to integrate into neurons and work long-term without triggering immune reactions.
In a rat model of chronic spinal cord injury, the treated animals showed significant, progressive improvements beginning several weeks after a single injection. The therapy not only reduced spasticity but also partially restored normal spinal reflex function and increased expression of the therapeutic genes in motor control neurons. The improvements were durable and measurable over extended periods.
Safety testing was equally rigorous. The researchers evaluated the treatment in multiple animal models—rats, pigs, and non-human primates—to ensure the therapy stayed confined to the targeted spinal cord region and caused no damage to motor or sensory function. Over up to 4.5 years of observation, no adverse effects were detected. This long safety window is crucial for a treatment meant to work for decades in human patients.
What makes this approach particularly promising is its simplicity and precision. A single administration targets only the affected spinal segment, avoiding the systemic effects and repeated doses that plague current treatments. The findings suggest this strategy could work not just for spinal cord injury but potentially for other neurological conditions involving abnormal muscle tone—conditions where the same GABA signaling breakdown occurs.
The path from animal studies to human trials typically takes years, but the foundation here is solid: clear mechanism, durable effect, and documented safety across multiple species. For the millions living with spinal cord injury, the possibility of regaining muscle control and movement from one treatment represents a genuine shift in what's medically possible. Marsala's team has shown that restoring one broken nerve signal can ripple through the entire system, giving muscles—and lives—a chance to work normally again.