PITTSBURGH, Feb. 5, 2025 – In a groundbreaking study published today in the esteemed journal Nature Medicine, researchers from the University of Pittsburgh School of Medicine have unveiled a novel, drug-free therapeutic approach that targets the fundamental causes of progression in spinal muscular atrophy (SMA), a devastating genetic neuromuscular disorder. This innovative intervention employs epidural electrical stimulation of sensory spinal nerves, which has shown promising potential in reactivating dormant motor neurons within the spinal cord. By doing so, it significantly enhances muscle strength and walking ability in adults afflicted by SMA.
The results emerge from a pilot clinical trial involving three adult volunteers diagnosed with varying degrees of SMA. Over a month-long period, regular sessions of targeted neurostimulation were administered, yielding notable improvements in motoneuron functionality, fatigue reduction, and marked enhancements in strength and ambulation. This pioneering research represents a significant leap forward, demonstrating for the first time that an engineered neurotechnology can counteract the degeneration of neural pathways and potentially restore cell function in a human neurodegenerative condition.
The complexity of SMA lies in its progressive nature, wherein the gradual deterioration of motor neurons culminates in severe physical limitations. “To effectively combat neurodegeneration, a dual approach is essential: halting the demise of neurons while rejuvenating the functionality of the surviving ones,” explained Dr. Marco Capogrosso, a leading researcher and assistant professor of neurosurgery at Pitt. This study posits a dual-pronged strategy that seeks to address the core issues of neural dysfunction, complementing existing neuroprotective therapies with a cutting-edge method that aims to restore neuronal capacity.
SMA is characterized by the gradual degeneration of motor neurons, the nerve cells responsible for controlling voluntary muscle movements. As motor neurons succumb to genetic mutations, patients experience debilitating muscle weakness and a range of motor deficits, including difficulties with locomotion, stair climbing, and even basic movements such as standing from a seated position. While therapeutic developments over the past decade, including gene replacement strategies and medications, have aimed to halt disease progression, this latest study aims to reverse the underlying neural deficits that contribute to SMA’s debilitating effects.
Prior research has indicated that the movement challenges associated with SMA can manifest before extensive motor neuron loss occurs, suggesting a critical role of spinal nerve circuit dysfunction in the disease’s initiation and symptomatology. Insights from previous animal model studies led by co-author Dr. George Mentis at Columbia University highlight that surviving motor neurons often receive diminished sensory feedback from nerve fibers returning information from the periphery to the central nervous system. Enhancing this feedback loop could improve the communication between the nervous system and muscles, potentially aiding voluntary movement and mitigating muscle wasting.
The researchers hypothesized that targeted epidural electrical stimulation could amplify sensory inputs directed toward motor neurons, which would reengage impaired neural circuits. These anticipated cellular modifications could translate into functional improvements in ambulatory capacity, offering hope not only for SMA patients but possibly also for individuals suffering from other neurodegenerative disorders.
Conducted as part of a pilot clinical trial, the study encompassed three adults diagnosed with milder forms of spinal muscular atrophy (Type 3 or 4). Participants underwent spinal cord stimulation (SCS) electrode implantation in the lower back, targeting sensory nerve roots exclusively. The treatment regimen involved five sessions per week over 29 days, with each session lasting approximately four hours, culminating in a total of 19 stimulation sessions.
Post-stimulation, the researchers executed a comprehensive battery of assessments, measuring variances in muscle strength, endurance, range of motion, fatigue levels, gait, and overall walking distance. These endpoints yielded illuminating results, evidencing functional improvements across various domains. Notably, all participants reported tangible benefits, with one patient expressing the newfound ability to walk unassisted from their residence to the research facility without succumbing to exhaustion.
Moreover, the study highlighted the capacity of neurostimulation to enhance participants’ scores on the 6-Minute Walk Test, a benchmark for measuring muscle endurance and fatigue. The study recorded an average increase of at least 20 meters amongst participants, starkly contrasting with a mean improvement of only 1.4 meters observed during a comparable three-month exercise program without spinal cord stimulation. Notably, patients who had undergone neuroprotective pharmacologic intervention for SMA over 15 months also experienced a median increase of just 20 meters, emphasizing the remarkable implications of electrical spinal cord stimulation.
The encouraging results reflected not only in functional assessments but also in the restored neural activity, signifying an increase in motor neurons’ capability to generate and relay electrical impulses to the muscles. As the research team elucidates, findings from this pilot study could pave the way for broader applications of neurostimulation techniques, extending beyond the domain of SMA treatment to include other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) or Huntington’s disease, contingent on identifying appropriate neural targets in forthcoming studies.
Dr. Robert Friedlander, chair of neurosurgery at Pitt and a co-director of the UPMC Neurological Institute, also emphasized the potential for this neurostimulation therapy to usher in new treatment avenues: “Our results paint an optimistic picture for the application of this approach in treating a range of neurodegenerative diseases, as we look forward to the next phase of clinical trials aimed at evaluating the long-term efficacy and safety of spinal cord electrical stimulation in SMA patients.”
The groundbreaking research is the culmination of collaborative efforts involving a multidisciplinary team, including co-first authors Dr. Genis Prat-Ortega, Scott Ensel, and Serena Donadio from Pitt, alongside another wave of contributors from prestigious institutions such as Carnegie Mellon University and Columbia University. This investigation was funded by an exploratory research grant from F. Hoffmann–La Roche, with patent applications filed by several authors related to this innovative work.
As the medical community fully comprehends the gravity of neurodegenerative diseases, this research opens new frontiers in enhancing the quality of life for individuals facing disabilities tethered to such conditions. It underscores a paradigm shift in approaching the treatment of neurodegeneration, focusing not only on therapeutic safeguards against neuronal loss but also on rejuvenating and restoring the functionality of existing neural circuitry.
The compelling narrative emerging from this study encapsulates the relentless pursuit of effective treatments by pioneering medical researchers. The findings herald a transformative direction in the management of spinal muscular atrophy and underline the importance of clinical innovation in the realm of neurodegenerative diseases.
Subject of Research: Epidural spinal cord stimulation in spinal muscular atrophy
Article Title: First-in-human study of epidural spinal cord stimulation in individuals with spinal muscular atrophy
News Publication Date: 5-Feb-2025
Web References:
References:
Image Credits: UPMC and Pitt Health Sciences
Keywords: Neurodegeneration, spinal muscular atrophy, electrical stimulation, motor neurons, neurostimulation therapy, clinical trial, functional improvement, muscle strength, neuromuscular diseases, neuroprotective treatments, spinal cord injury, nerve function restoration.
Tags: clinical trial spinal cord stimulationdrug-free neuromuscular interventionsenhancing muscle strength in SMAepidural electrical stimulation benefitsinnovative therapies for motor neuron disordersmotor neuron reactivation techniquesNeurodegenerative disease researchneurotechnology advancements in medicinerestoring neural function in adultsspinal cord stimulation therapySpinal muscular atrophy treatmentUniversity of Pittsburgh SMA study
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