GENE THERAPY APPROACHES TO ENHANCING PLASTICITY AND REGENERATION AFTER SPINAL CORD INJURY

Exp Neurol, 2012 · DOI: 10.1016/j.expneurol.2011.01.015 · Published: May 1, 2012

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

This review discusses how gene therapy can be used to promote the regeneration of nerve fibers and the rearrangement of neural circuits after a spinal cord injury. Gene therapy can help address the limited ability of injured neurons to regenerate and can also help researchers identify factors that are important for nerve fiber growth. Genetic approaches can be used to modify the environment around injured nerve fibers by expressing growth factors, enhancing sprouting and regeneration, and guiding the regenerating fibers towards their targets.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Injured axons remain responsive to neurotrophic factor delivery, even in chronic stages of injury, responding with enhanced neuronal survival and axon growth.
2
Transient neurotrophic factor expression within a lesion site is sufficient to induce axonal growth, but is not required to sustain regenerated axons within a site of spinal cord injury.
3
Gradients of NT-3 have been shown to promote axonal bridging across a cervical lesion site.

Research Summary

Regeneration and structural plasticity are regulated by a delicate balance of growth-promoting and growth-inhibiting influences in the injured adult mammalian central nervous system (CNS). Gene therapy might be one means to accomplish some of these goals. The translation of animal studies will therefore advance with improved vector and promoter systems for minimally invasive administration and targeted, localized, cell-specific and regulated gene delivery.

Practical Implications

Localized Growth Factor Delivery

Autologous or syngeneic cells genetically modified by viral vectors can serve as biological minipumps for the localized, targeted delivery of growth factors into a lesion site.

Temporal Regulation of Gene Expression

The ability to turn gene expression off after axons have entered a lesion site might enhance the efficacy and safety of growth factor gene delivery.

Targeted Gene Delivery

Retrograde viral transport together with cell-specific promoters might allow for cell specific gene expression in motor neurons to chemotropically attract descending fibers.

Study Limitations

1
Limited intrinsic regenerative capacity of injured neurons.
2
Inhibitory environment around a spinal cord lesion site.
3
Lack of axonal growth across a lesion site due to continuous supply of growth factors within the lesion site.

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