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(61) Spinal Cord Stimulation Improves Motorneuron Function in Three Humans with Spinal Muscular Atrophy

Friday, June 13, 2025
5:10 PM - 5:50 PM ET
Location: Grand Foyer
Introduction: Spinal muscular atrophy (SMA) is characterized by motor neuron dysfunction and death, leading to impaired motor control. This study investigates the potential of epidural spinal cord stimulation (SCS) to stimulate the sensory afferents and restore motoneuron function and improve motor performance in individuals with SMA. Preclinical works demonstrate that SMA motor neurons show low firing rates because of loss of excitatory input from primary sensory afferents1,2,3. We hypothesized that electrical stimulation of the sensory afferents would improve motorneuron dysfunction.

Methods: Three participants with type III SMA underwent SCS treatment over 29 days. Motor performance was assessed using gait, and strength analysis while motor neuron properties were assessed with high-density electromyography (HDEMG), transcranial magnetic stimulation (TMS), and task-based functional magnetic resonance imaging (fMRI). Changes in performance were measured by immediate assistive effects same day SCS ON vs OFF), and therapeutic effects (pre-implant vs post-explant study with SCS OFF).

Results: SCS significantly improved both strength and gait measures after just 4 weeks of use. Gait analysis indicated significant improvements in stride length, stride velocity, and range of motion, with these therapeutic gains persisting even after SCS was turned OFF (Figure 1). SCS also led to improvements in strength (up to +180%) with SCS turned off. As for motor neuron properties HDEMG revealed the emergence of 'rescued' motor units, exhibiting firing patterns similar to those of able-bodied individuals. Additionally, spinal cord fMRI showed increased BOLD activation in regions corresponding to quadricep motoneurons post-SCS, supporting long term therapeutic effects through enhanced neural activity (Figure 2). Lastly TMS showed a reduction of the hyperexcitability of SMA motor neurons indicating a direct change of the motor neuron membrane properties.

Conclusion: For the first time we show SCS effectively reverses motoneuron dysfunction in SMA, leading to sustained improvements in motor control and strength. These findings suggest that SCS could serve as a promising therapeutic intervention for SMA, offering both immediate assistive benefits and long-term therapeutic gains. Further studies with larger cohorts are warranted to validate these results and explore the synergistic potential of combining SCS with existing pharmacological treatments.