Anti-Nogo-A NG101 treatment induces changes in spinal cord micro- and macrostructure following spinal cord injury
NG101 is a recombinant antibody that neutralizes the nerve growth inhibitor Nogo-A, promoting neural repair and improving upper extremity motor function in spinal cord injury (SCI). This study evaluated spinal cord MRI biomarkers to detect treatment-related structural changes and enhance patient stratification using data from 106 participants with acute cervical SCI in the phase 2b NISCI trial. We assessed lesion volume, tissue bridges, and remote changes in cross-sectional cord area (CSA), and tract-specific myelin-sensitive magnetization transfer saturation (MTsat) over six months. Compared to placebo, NG101-treated participants exhibited faster lesion volume reduction and a slower decline of CSA and MTsat in the corticospinal tracts and dorsal columns. Crucially, multimodal stratification incorporating MRI and electrophysiological measures substantially enhanced the detection of clinical treatment effects. These findings suggest NG101 slows trauma-induced progressive macro- and microstructural degeneration or promotes fiber sprouting. Combining MRI with electrophysiology enables sensitive detection of treatment effects and efficient trial designs. ClinicalTrials.gov identifier: NCT03935321.
Authors
- Michèle Hubli (ORCID: https://orcid.org/0000-0001-6054-3283)
- Andreas Badke (ORCID: https://orcid.org/0000-0003-0577-2248)
- Margret Hund‐Georgiadis (ORCID: https://orcid.org/0000-0002-4415-2888)
- Mirko Aach (ORCID: https://orcid.org/0000-0002-9333-5912)
- Tim Killeen (ORCID: https://orcid.org/0000-0001-8246-4957)
- Kiomars Sharifi
- Maryam Seif (ORCID: https://orcid.org/0000-0002-9253-5680)
- Alan J. Thompson (ORCID: https://orcid.org/0000-0002-4333-8496)
- Kerstin Rehahn
- M.F. Bolliger
- Lynn Farner (ORCID: https://orcid.org/0009-0004-8252-5448)
- Martin E. Schwab
- Marion Saur
- Klaus Röhl
- Armin Curt
- Tim M. Emmenegger (ORCID: https://orcid.org/0000-0003-0350-3482)
- Rainer Abel (ORCID: https://orcid.org/0000-0002-8328-8438)
- the Nogo Inhibition in Spinal Cord Injury (NISCI) Study Group
- Rüdiger Rupp (ORCID: https://orcid.org/0000-0002-3873-1023)
- Jesús Benito
- Doris Maier (ORCID: https://orcid.org/0000-0002-3261-2381)
- Michael Baumberger
- Patrick Freund (ORCID: https://orcid.org/0000-0002-4851-2246)
- Jiri Kriz
- Martin Schubert (ORCID: https://orcid.org/0000-0003-4495-6533)
- Paulina S. Scheuren (ORCID: https://orcid.org/0000-0001-7568-0133)
- Norbert Weidner (ORCID: https://orcid.org/0000-0002-1447-8967)
- Nikolaus Weiskopf (ORCID: https://orcid.org/0000-0001-5239-1881)
Institutions
- University of British Columbia (CA)
- Queen Mary University of London (GB)
- University of Zurich (CH)
- Charles University (CZ)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Bayreuth Medical Center (DE)
- BG Klinik Tübingen (DE)
- Institute for Biomedical Engineering (CH)
- University Hospital in Motol (CZ)
- Berufsgenossenschaftliche Unfallklinik Murnau (DE)
- Swiss Paraplegic Center (CH)
- Universitätsklinik Balgrist (CH)
- International Collaboration On Repair Discoveries (CA)
- Max Planck Institute for Human Cognitive and Brain Sciences (DE)
- Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES)
- BG University Hospital Bergmannsheil Bochum (DE)
- The London College (GB)
- BG Klinikum Bergmannstrost Halle (DE)
- Diagnostic and Treatment Centre Berlin (DE)
- Swiss Paraplegic Research (CH)
- University College London (GB)
- Medical University of Vienna (AT)
- Leipzig University (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-12
- DOI
- https://doi.org/10.1038/s41467-026-71412-0
- Primary Topic
- Nerve injury and regeneration
- Type
- article
- Field-Weighted Citation Impact
- 0.00