From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Neural Regen Res, 2025 · DOI: https://doi.org/10.4103/NRR.NRR-D-23-01928 · Published: March 1, 2025

Spinal Cord Injury Pharmacology Regenerative Medicine & Stem Cells

Simple Explanation

Spinal cord injury (SCI) leads to various disabilities and complications, affecting not only the injured individuals but also their families and communities, creating financial burdens. Current treatments often target only one aspect of the injury's secondary mechanisms, which limits their effectiveness. Combining multiple therapeutic agents that address different injury mechanisms could lead to synergistic beneficial effects, enhancing structural and functional restoration of the damaged spinal cord. This review summarizes current trends in using simultaneous or sequential strategies that combine therapeutic agents for SCI treatment. Examples of combined therapeutic strategies include rehabilitation, electric stimulation, biomaterials, drugs, cells, and neurotrophins. These combinations can synergistically improve neuroprotection, enhance axonal regeneration and remyelination, and reduce fibro-glial scarring.

Study Duration

Not specified

Participants

Patients with SCI in reviewed clinical trials

Evidence Level

Review article

Key Findings

1
The combination of melatonin and dexamethasone showed suitable neuroprotective activities by reducing neutrophil infiltration, cytokine levels, tissue damage, inducible nitric oxide synthase expression, and apoptosis in SCI-treated mice, and motor recovery was also ameliorated.
2
Autologous co-transplantation of olfactory ensheathing cells and bone marrow mesenchymal stem cells (MSCs) in patients with chronic complete thoracic SCI has shown safety and some improvement in functional capacity.
3
A combination of small molecules (LDN193189, SB431542, CHIR99021, and P7C3-A20) loaded inside an injectable collagen hydrogel promoted neurogenesis, inhibited astrogliogenesis, and induced neurons to migrate into the core of the non-neural lesion, causing some recovery of locomotion.

Research Summary

Spinal cord injury (SCI) results in permanent neurological disability and poses significant physical, financial, and psychological challenges. The complexity of SCI pathophysiology necessitates exploring combined therapeutic strategies to target multiple injury mechanisms. Combined therapeutic strategies, including drugs, cells, biomaterials, and electrical stimulation, have shown potential in improving neuroprotection, axonal regeneration, and functional outcomes in SCI models. These approaches aim to address the limitations of single treatments by acting synergistically. Future research should focus on carefully selecting and testing combined therapeutic agents that act synergistically, considering the magnitude and location of SCI. Clinical trials should be conducted to evaluate the safety and efficacy of these strategies in patients with complete SCI across different stages of injury.

Practical Implications

Enhanced Neuroprotection

Combining drugs that target oxidative stress, excitotoxicity, apoptosis, and inflammation can enhance neuroprotection in the acute phase of SCI.

Improved Axonal Regeneration and Remyelination

Staggered administration of agents that promote axonal regeneration, remyelination, and reduction of fibro-glial scarring can improve long-term functional outcomes.

Personalized Treatment Strategies

Careful selection of therapeutic agents based on the individual's SCI characteristics, such as magnitude and location, is crucial for optimizing treatment outcomes.

Study Limitations

1
Animal models may not fully replicate the complexity of SCI in humans.
2
Many therapeutic strategies have shown promise in preclinical studies but have had limited success in clinical trials.
3
Complete SCI remains challenging, and a universal standard treatment is still needed.

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