Spinal cord stimulation restores neurological function and targets important features of progressive neurodegenerative diseases

Early results from a pilot clinical trial of three human volunteers with SMA showed that a 1 month regular nerve stimulation session improves motor neuron function, reduces fatigue, and all symptom severity It shows that participants will improve their strength and walk. This study first shows that neuroengineering can be designed to reverse neural circuit degeneration and rescue cell function.

“To combat neurodegeneration, there are two things to do: stop neuronal death and restore the function of surviving neurons,” says the author, PhD, PhD, assistant professor in Neurosurgery at Pitt. Marco Capogrosso said. “This study proposed an approach to treating the root causes of neural dysfunction, complementing existing neuroprotective therapy to reverse neuronal dysfunction.”

SMA is a genetic neurodegenerative disease that manifests in progressive death and functional decline of motor neurons. These are neurons that control movement by transmitting signals from the brain and spinal cord to the muscles. Over time, loss of motor neurons gradually causes muscle weakness, leading to a variety of movement disorders, including participants in this trial, difficulty walking, climbing stairs, and rising from a chair.

Although there is no treatment for SMA, several promising neuroprotective therapies have become available over the past decade. These include gene replacement therapy and drugs. Both stimulate the production of proteins that support motor neurons that prevent neuron death and conversely prevent them from suppressing them.

Studies suggest that lack of exercise in SMA appears before widespread motor nuclei death, and that underlying dysfunction of spinal neural circuits may contribute to the onset of disease and the development of symptoms. According to previous research into animal models of SMA by co-author Dr. George Mentis, surviving motor neurons provide less stimulation input from sensory nerves – fibers that return information from the skin and muscles are the central nervous system . Therefore, compensates for this deficit in neural feedback can improve communication between the nervous system and the muscles, help muscle movement, and promote muscle wasting.

Pitt researchers can use targeted epidural electrostimulation therapy to save the lost cell function of neurons by amplifying sensory inputs into motor neurons and engaging in degenerated neural circuits. I assumed that. These cellular changes can be converted into functional improvements in migration capabilities.

The PITT study was conducted as part of a pilot clinical trial that enrolled three adults in mild form of SMA (type 3 or 4 SMA). During the 29-day study period, participants were confined to two spinal cord stimulation (SCS) electrodes and placed in the lumbar region on both sides of the spinal cord, directing stimulation only to the roots of the sensory nerves. Each test session lasted 4 hours and was conducted five times a week for a total of 19 sessions until the stimulator was visible.

After confirming that the stimulation acted as intended spinal motor neurons, the researchers conducted a series of tests to measure muscle strength and fatigue, changes in walking, range of motion and within walking distance, and motor nuclear function. I did.

“SMA is a progressive disease, so patients don't think they get better over time. However, that's not what we saw in our study. Over the course of four weeks of treatment, our study participants were active. Improved with several clinical outcomes with improvements. For example, towards the end of the study, one patient reported that he could walk to the lab without losing fatigue, rehabilitation in the pit.

All participants increased their 6-minute walk test score (a measure of muscle endurance and fatigue) at least 20 meters. 20 meters after 15 months of SMA-specific neuroprotective pharmacological therapy.

These functional benefits were reflected by improved neural function, including an improved ability of motor neurons to generate electrical impulses and transmit them to the muscles.

“Our results suggest that this neurostimulation approach can be widely applied to treat other neurodegenerative diseases beyond SMA, such as ALS and Huntington's disease. MD, Chairman of Neurosurgery at PITT; Co-director of the UPMC Neurological Institute. “We hope to continue working with SMA patients and launch another clinical trial to test the long-term efficacy and safety of electrospinal stimulation.”

This study was based on F. It was supported by an exploratory research grant from Hoffmann-La Roche. Genentech, Inc. (Member of the Roche Group) and the University of Pittsburgh retain IP rights related to this study. Marco Capogrosso, Genis Prat-Ortega and Mikael Eliasson hold patent applications related to this work.