Elamipretide (SS-31) promotes recovery by preserving mitochondrial bioenergetics and neural remodeling after spinal cord injury
Song Z, Ban Z, Zhao H, Mei X
Neurochemistry International (2026)
In a mouse thoracic contusion model of spinal cord injury, the mitochondria-targeting peptide elamipretide (SS-31) improved locomotor recovery and gait performance, reduced lesion pathology, attenuated early apoptotic signaling (lower cleaved caspase-3 / Bax, higher Bcl-2), diminished chronic-stage astrogliosis, and preserved mitochondrial membrane potential plus oxidative-phosphorylation protein integrity in oxidatively stressed PC12 cells.
Song and colleagues at Jinzhou Medical University investigated whether elamipretide (SS-31), a mitochondria-targeting tetrapeptide, improves functional outcomes after contusive spinal cord injury in mice. The work combines an in-vivo thoracic-contusion SCI model with in-vitro mechanistic experiments in oxidatively stressed PC12 cells.
In vivo: SS-31 treatment significantly enhanced locomotor recovery and gait performance compared with vehicle. Histological analyses showed reduced lesion pathology and increased neuronal preservation in the injured spinal cord. Early after injury, SS-31 attenuated apoptosis signaling — reduced cleaved caspase-3 and Bax, increased Bcl-2. At the chronic stage, SS-31 was associated with diminished astrogliosis and enhanced markers of axonal and synaptic remodelling.
In vitro: in oxidatively stressed PC12 cells (a neuronal-like cell line), SS-31 preserved mitochondrial membrane potential, reduced reactive oxygen species accumulation, and supported oxidative-phosphorylation-related protein integrity.
The authors frame the findings as evidence that SS-31's neuroprotective effects after SCI are mediated by mitigation of early apoptotic injury combined with support for mitochondrial homeostasis and chronic-stage neural remodeling.
This is a preclinical mouse study and a parallel cell-line experiment; SCI clinical trials of elamipretide have not been reported and the translational pathway to human SCI therapy is unestablished. The thoracic contusion model is one of several SCI models; effect sizes and the duration of the protective signal in cervical injury or transection models are not addressed.
The abstract does not report sample sizes per arm, dosing details for SS-31, or the timing of administration relative to injury — early versus delayed administration matters substantially in SCI translation. Locomotor recovery is reported qualitatively as "significantly enhanced" without an effect size or scoring system specified in the abstract.
PC12 cells are an immortalised pheochromocytoma-derived line widely used as a neuronal surrogate but are not primary neurons. The astrogliosis and synaptic remodelling claims at the chronic stage are intriguing but the chronic timepoint is not specified. Abstract-only extraction.
SS-31's principal human clinical evidence remains in primary mitochondrial myopathy. There is no SS-31 SCI clinical trial.
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