| Endogenous stem cells |
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Limited endogenous neural progenitor/stem cell (NPSC) population derived from radial and tanycyte ependymal cells in the central canal, which are primarily astroglially-biased in differentiation.
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Genetic manipulation can bias NSPCs towards oligodendytic or neuronal fates.
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Clinical trial examining endothelin B receptor agonist drug, Sovateltide (NCT04054414), may help to activate endogenous NPSCs.
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| IPSC-derived NPCs |
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IPSC-derived NPCs can be developed through dual SMAD inhibition to obtain tripotent NPCs.
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Biasing of NPCs prior to transplantation to oligodendrogenic, motor neuron, or interneuronal fates may help enhance myelination and restore motor function.
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| Direct cell reprogramming |
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With a high proportion of astrocytes in the lesion epicenter, direct cell reprogramming of astrocytes to neurons through various means – small molecules/pharmacological approaches, overexpression of transcription factors, CRISPR/Cas9 modulation of transcription factors – has been examined.
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| Scaffolds and stem cells |
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Bioresorbable scaffolds, provided in combination with transplanted cells, aim to provide a temporary ECM to graft new cells and/or provide localized growth factors.
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Collagen-based scaffold (NeuroRegen) [NCT02688049, NCT02510365, NCT02352077] and PLGA-PLL-based scaffold (Neuro-Spinal) [NCT02138110; NCT03762655] are being tested in clinical trials, with no observed adverse effects and some motor improvements.
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Preclinical work is examining other potential scaffolds, such as self-assembling peptide QL6 and a hyaluronan-methylcellulose hydrogel (HAMC).
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| Noncellular strategies |
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| Early surgery |
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| Hemodynamic regulation |
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Current guidelines recommend a MAP of 85 and 90 mm Hg be maintained for 7 d post-SCI.
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Spinal cord perfusion pressure (SCPP) may be a better predictor of outcomes compared to MAP. It is recommended to maintain SCPP above 50 mm Hg.
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| Targeted rehabilitation and functional electrical stimulation |
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Targeted rehabilitation strategies aim to improve patient independence and activities of daily living.
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Combined rehabilitation and electrical stimulation paradigms may further augment recovery.
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Recent benefits demonstrated for rehabilitation on promoting stem cell graft integration after SCI in animal models.
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| Riluzole |
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Sodium-channel blocking drug that helps to mitigate glutamate-associated excitotoxic effects post-SCI, has been tested in Phase I trial with no serious adverse effects following administration in acute SCI (NCT00876889).
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Phase IIB/III trial halted due to slow enrolment (NCT01597518).
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Current trial with unknown status examining the effect of riluzole in reducing spasticity in chronic SCI (NCT02859792).
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| Anti-Nogo-A Antibody |
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Nogo-A is a myelin-associated neuronal growth inhibitory protein.
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Anti-Nogo-A antibodies have demonstrated improvements in locomotion, dexterity, axonal sprouting, with good tolerability in humans.
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Clinical trials (NCT0398944 and NCT03935321) are examining anti-Nogo in chronic and acute SCI respectively.
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| Anti-RGMa Antibody |
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RGMa contributes to inhibition of axonal growth.
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Anti-RGMa has been shown to improve neuronal growth as well as locomotion and is being tested in a current clinical trial (NCT04295538), with expanded access also approved (NCT04278235).
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