Researchers at the University of Pittsburgh School of Medicine say a new, drug-free, minimally invasive intervention can target the root cause of neural function loss.
The intervention targets the root cause of progressive loss of neural function in spinal muscle atrophy (SMA), an inherited neuromuscular disease. It involves electrical stimulation of the sensory spinal nerves, gradually reawakening functionally silent motor neurons in the spinal cord. This can, in turn, improve leg muscle strength and walking in adults with SMA.
Researchers published their findings in Nature Medicine. Early outcomes in three human volunteers showed that one month of regular neurostimulation sessions improved motoneuron function, reduced fatigue and improved strength and walking in all participants, regardless of the severity of their symptoms.
According to a Pitt press release, the study marks the first time researchers showed that a neurotechnology can be engineered to reverse degeneration of neural circuits and rescue cell function in a human neurodegenerative disease.
The Pitt team set out to address underlying dysfunction in spinal nerve circuitry that may contribute to SMA onset and symptom development. Early research on animal models conducted by study co-author George Mentis of Columbia University observed that surviving motor neurons receive fewer stimulation inputs from sensory nerves. Compensating in this deficit could improve communication between the nervous system and the muscles, according to Pitt. That would aid muscle movement and combat muscle wasting.
Pitt researchers figured a targeted epidural electrical stimulation therapy could rescue lost nerve sell function by amplifying sensory inputs to the motor neurons and engaging the degenerated neural circuits. This could, they believe, translate into functional improvements in movement capacity.
Over the course of 29 days, the participants received two spinal cord stimulation (SCS) electrode implants placed in the lower back region on each side of the spinal cord. They directed the stimulation exclusively to sensory nerve roots. Testing sessions lasted four hours each, taking place five times per week for a total of 19 sessions before device explantation.
The team confirmed that the stimulation worked as intended, then performed tests to measure muscle strength and fatigue, changes in gait, range of motion and walking distance and motoneuron function.
All participants increased their 6-Minute Walk Test Score by at least 20 meters. That compared to a mean improvement of 1.4 meters over three months of comparable exercise regimen unaided by SCS and a median increase of 20 meters after 15 months of SMA-specific neuroprotective pharmacologic therapy. The researchers also report improved neural function. That included a boost in motoneurons’ capacity to generate electrical impulses and transmit them to the muscles.
“Our results suggest that this neurostimulation approach could be broadly applied to treat other neurodegenerative diseases beyond SMA, such as ALS or Huntington’s disease, as long as appropriate cell targets are identified in the course of future research,” said co-corresponding author Dr. Robert Friedlander, chair of neurosurgery at Pitt and co-director of the UPMC Neurological Institute. “We are hoping to continue working with SMA patients and launch another clinical trial to test the long-term efficacy and safety of electrical spinal cord stimulation.”
