Nerves are made up of bundled axons, the long connections between neurons, and so regeneration following injury involves new axons finding their way across the area of damage as they regrow, a process hampered in mammalian species by the formation of scar tissues. The antibody NG101 has long been known to promote regrowth of nerve tissue following damage. It has been a long road from the initial discovery a few decades ago to a recent clinical trial in patients with spinal cord injury. That trial allowed more data to be gathered on the regeneration process via imaging approaches, and researchers made use of the opportunity to examine in more detail as to how NG101 enhances regeneration in humans. Unlike animal studies where histology and dissection of nerve tissue is possible, human studies must rely on imaging, and those imaging techniques must be developed as trials progress.
One promising therapeutic strategy to enhance axonal plasticity is the inhibition of Nogo-A, a potent neurite growth suppressive membrane protein in central nervous system (CNS) myelin and neuronal membranes. Preclinical studies show that NG101, a humanized monoclonal antibody targeting Nogo-A, promotes axonal sprouting and functional recovery. Recent exploratory findings from a phase 2b clinical trial suggest that NG101 may also improve upper extremity motor function in participants with motor incomplete cervical spinal cord injury (SCI), supporting the translational potential of Nogo-A inhibition.
To better understand how Nogo-A inhibition influences structural recovery in human SCI, and to sensitively track potential regenerative effects, objective in vivo biomarkers are needed. Cross-sectional cord area (CSA) is a robust macroscopic marker of spinal cord atrophy, reflecting structural loss from axonal degeneration and demyelination, secondary to traumatic SCI and correlating with clinical impairment. Microstructural imaging provides reproducible metrics such as magnetization transfer saturation (MTsat), which is sensitive to myelin content and enables detection of demyelination and remyelination of spinal fiber tracts.
No study has yet assessed how macro- and microstructural Magnetic Resonance Imaging (MRI) biomarkers respond to a targeted neuroregenerative treatment in acute cervical SCI, or how these measures can be combined to optimize trial design. In this study, we investigated whether CSA and MPM-derived indices can track NG101-induced structural effects. 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.
Link: https://doi.org/10.1038/s41467-026-71412-0
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