A promising new electrical stimulation therapy for spinal muscular atrophy (SMA) has shown significant improvements in reactivating motor neurons and enhancing movement capabilities. In a pilot clinical trial, three participants received spinal cord stimulation for one month, resulting in increased strength, reduced fatigue, and improved walking ability.
Minimally Invasive Treatment for SMA
Researchers from the University of Pittsburgh School of Medicine have developed a novel, drug-free, minimally invasive treatment aimed at addressing the root cause of progressive neural decline in SMA. This genetic neuromuscular disease involves the gradual death and functional degeneration of motor neurons. The new approach uses electrical stimulation of sensory spinal nerves to reactivate dormant motor neurons in the spinal cord, thereby improving leg muscle strength and walking ability in adults with SMA.
This breakthrough is detailed in a recent Nature Medicine publication.
Results of the Pilot Clinical Trial
In the pilot clinical trial involving three SMA patients, one month of regular neurostimulation sessions led to enhanced motor neuron function, reduced fatigue, and improved muscle strength and walking ability. This study represents the first instance of neurotechnology specifically targeting and reversing neural circuit degeneration in a human neurodegenerative disease.
“Counteracting neurodegeneration requires halting neuron death and restoring function to surviving neurons,” explained Dr. Marco Capogrosso, assistant professor of neurosurgery at Pitt. “Our approach treats the root cause of neural dysfunction, complementing existing neuroprotective treatments with a new method that restores nerve cell function.”
Understanding SMA
Spinal muscular atrophy (SMA) is a genetic disorder characterized by the progressive death and functional decline of motor neurons. These neurons control movement by transmitting signals from the brain and spinal cord to the muscles. The loss of motor neurons leads to muscle weakness and motor deficits, including difficulties with walking, climbing stairs, and standing up.
While there is no cure for SMA, recent advancements in neuroprotective treatments have emerged, including gene replacement therapies and medications that stimulate the production of motoneuron-supporting proteins to mitigate neuronal death and slow disease progression.
Theoretical Basis of the Study
Research indicates that movement impairments in SMA occur before extensive motor neuron loss, suggesting a role for dysfunction in spinal nerve circuitry in disease onset and progression. Studies by George Mentis, Ph.D., at Columbia University show that surviving motor neurons in SMA receive decreased stimulation inputs from sensory nerves—fibers that transmit information from the skin and muscles to the central nervous system. Enhancing these sensory inputs could improve nervous system-muscle communication, aid movement, and combat muscle atrophy.
Pitt researchers hypothesized that targeted epidural electrical stimulation therapy could rescue lost nerve cell function by amplifying sensory inputs to motor neurons and engaging degenerated neural circuits. Such cellular improvements should translate into functional movement gains.
Methodology of the Study
The Pitt study involved a pilot clinical trial with three adults having milder SMA forms (Types 3 or 4 SMA). Participants were implanted with spinal cord stimulation (SCS) electrodes in their lumbar region, stimulating exclusively sensory nerve roots. Testing sessions, lasting four hours each, were conducted weekly, totaling 19 sessions over 29 days.
Post-stimulation, researchers conducted tests measuring muscle strength, fatigue, gait changes, range of motion, walking distance, and motoneuron function.
Positive Outcomes
Patients in the study demonstrated significant improvements in movement capabilities over the four-week treatment period. Elvira Pirondini, Ph.D., assistant professor of physical medicine and rehabilitation, noted, “Despite SMA’s progressive nature, our study participants showed improvement in multiple clinical outcomes and daily activities. One patient reported walking from home to the lab without fatigue by the study’s end.”
All participants showed enhanced performance in the 6-Minute Walk Test, indicating improved muscle endurance and decreased fatigue. The results were striking, with improvements surpassing those seen in other therapies over longer periods.
Implications and Future Directions
These promising findings suggest that this neurostimulation approach may have widespread applications for treating other neurodegenerative diseases, such as ALS or Huntington’s disease, with appropriate targeting in future research.
“We aim to continue working with SMA patients and conduct further clinical trials to evaluate the long-term efficacy and safety of electrical spinal cord stimulation,” said Robert Friedlander, M.D., chair of neurosurgery at Pitt and co-director of the UPMC Neurological Institute.
Conclusion
This groundbreaking study demonstrates a significant step forward in treating SMA by targeting the root cause of neuronal dysfunction. The encouraging results not only offer hope to SMA patients but also open avenues for advancing treatments in other neurodegenerative disorders.
If you find this article insightful, we encourage you to leave a comment below, share it on social media