Evidence map›Paper›PMID 39910271›Full record

Trial reportNature medicine2025

First-in-human study of epidural spinal cord stimulation in individuals with spinal muscular atrophy.

Genís Prat-Ortega, Scott Ensel, Serena Donadio, Luigi Borda, Amy Boos, Prakarsh Yadav, Nikhil Verma, Jonathan Ho, Erick Carranza, Sarah Frazier-Kim and 15 more

Registry-linked trialAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05430113 (Spinal Cord Stimulation for the Treatment of Motor Deficits in People With Spinal Muscular Atrophy), which is not on this map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05430113 nacompletednot on this map

Spinal Cord Stimulation for the Treatment of Motor Deficits in People With Spinal Muscular Atrophy

TypeinterventionalSponsorMarco CapogrossoRan2022 to 2025Enrolled3ConditionsSpinal Muscular Atrophy Type 3, Spinal Muscular Atrophy Type 4ArmsSpinal Cord Stimulator (octopolar Medtronic Vectris Leads)
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Genís Prat-Ortega *Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-3401-3569
Scott Ensel *Rehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, PA, USA.
Serena Donadio *Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Luigi BordaDepartment of Mechanical engineering, Carnegie Mellon University, Pittsburgh, PA, USA.ORCID http://orcid.org/0009-0003-4670-8530
Amy BoosRehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, PA, USA.
Prakarsh YadavDepartment of Mechanical engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
Nikhil VermaDepartment of Mechanical engineering, Carnegie Mellon University, Pittsburgh, PA, USA.ORCID http://orcid.org/0009-0004-5533-6887
Jonathan HoDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Erick CarranzaRehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, PA, USA.
Sarah Frazier-KimDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0009-0004-8558-1883
Daryl P FieldsDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Lee E FisherRehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-9072-3119
Doug J WeberDepartment of Mechanical engineering, Carnegie Mellon University, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-9782-3497
Jeffrey BalzerDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Tina DuongDepartment of Neurology and Clinical Neurosciences, Stanford University, Palo Alto, CA, USA.
Steven D WeinsteinGenentech Roche, San Francisco, CA, USA.
Mikael J L EliassonGenentech Roche, San Francisco, CA, USA.
Jacqueline MontesDepartment of Rehabilitation and Regenerative Medicine, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0002-7357-0819
Karen S ChenSpinal Muscular Atrophy Foundation New York, New York, NY, USA.
Paula R ClemensDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-0652-6703
Peter GersztenDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
George Z MentisCenter for Motor Neuron Biology and Disease, Columbia University, New York, NY, USA.
Elvira PirondiniRehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, PA, USA. elvirap@pitt.edu.ORCID http://orcid.org/0000-0002-8078-3951
Robert M FriedlanderDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA. friedlanderr@upmc.edu.ORCID http://orcid.org/0000-0002-5008-7592
Marco CapogrossoDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA. mcapo@pitt.edu.ORCID http://orcid.org/0000-0002-0975-316X

Funding

Mechanisms of Central Synaptic Dysfunction in SMAR01NS078375 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI George Z Mentis · 2012 to 2026
$6.6M
Mechanisms of synaptic loss by the classical complement pathway in motor circuit development and diseaseR01AA027079 · NIAAA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MENTIS, GEORGE Z · 2018 to 2022
$3.2M
NIAAA NIH HHS R01 AA027079NINDS NIH HHS R01 NS078375
6 · The paper itself

Abstract

Spinal muscular atrophy (SMA) is an inherited neurodegenerative disease causing motoneuron dysfunction, muscle weakness, fatigue and early mortality. Three new therapies can slow disease progression, enabling people to survive albeit with lingering motor impairments. Indeed, weakness and fatigue are still among patients' main concerns. Here we show that epidural spinal cord stimulation (SCS) improved motoneuron function, thereby increasing strength, endurance and gait quality, in three adults with type 3 SMA. Preclinical works demonstrated that SMA motoneurons show low firing rates because of a loss of excitatory input from primary sensory afferents. In the present study, we hypothesized that correcting this loss with electrical stimulation of the sensory afferents could improve motoneuron function. To test this hypothesis, we implanted three adults with SMA with epidural electrodes over the lumbosacral spinal cord, targeting sensory axons of the legs. We delivered SCS for 4 weeks, 2 h per day during motor tasks. Our intervention led to improvements in strength (up to +180%), gait quality (mean step length: +40%) and endurance (mean change in 6-minute walk test: +26 m), paralleled by increased motoneuron firing rates. These changes persisted even when SCS was turned OFF. Notably, no adverse events related to the stimulation were reported. ClinicalTrials.gov identifier: NCT05430113 .

Indexed as

Muscular Atrophy, SpinalSpinal CordSpinal Cord StimulationAdultFemaleGaitHumansMaleMiddle AgedMotor Neurons

Identifiers

PMID39910271
PMCPMC13000922

What Socratic holds

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Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.