Spinal Cord Injury: Time to Move?

The Journal of Neuroscience, 2007 · DOI: 10.1523/JNEUROSCI.3444-07.2007 · Published: October 31, 2007

Spinal Cord Injury Regenerative Medicine Neuroplasticity

Simple Explanation

This symposium summarizes scientific evidence for current or planned clinical trials for spinal cord injury (SCI) patients. After SCI, primary and secondary damage occurs and several endogenous processes are triggered that may foster or hinder axonal reconnection from supralesional structures. Animal studies indicate these processes can be enhanced or decreased by interventions, like drugs that reduce repulsive barriers (anti-Nogo, anti-Rho) or cell grafts to enhance immunological mechanisms or remyelinate axons. Rehabilitative approaches combined with neurobiological approaches may produce significant functional recovery by ensuring optimal function of endogenous spinal networks and establishing new dynamic interactions with supralesional structures.

Study Duration

Not specified

Participants

Animal models and human clinical trials

Evidence Level

Review/Symposium

Key Findings

1
Function-blocking antibodies recognizing Nogo-A induce enhanced regenerative sprouting from injured fibers, long-distance regeneration of subpopulations of fibers, and enhanced compensatory fiber growth from non-injured fibers and tracts.
2
A well-controlled innate and adaptive immune response is pivotal for repair, and that not only macrophages are needed but that other immune cells also participate in the network of functions needed for repair.
3
After partial spinal injuries, the expression of the hindlimb locomotor pattern could primarily be attributable to the intrinsic reorganization and re-expression of the spinal locomotor CGP below the lesion.

Research Summary

This symposium summarizes scientific bases for current clinical trials aimed at improving functions after SCI. After primary and secondary damage, endogenous processes may foster or hinder axonal reconnection. Animal studies show these processes can be enhanced/decreased by drugs to diminish repulsive barriers or increase regeneration/sprouting. Cellular replacement can enhance immunological mechanisms or remyelinate axons. Rehabilitative approaches based on functional networks below the lesion combined with neurobiological approaches may produce significant recovery of functions like locomotion by allowing a new dynamical configuration between circuits and spinal mechanisms.

Practical Implications

Clinical Trials for Nogo-A Antibodies

Anti-Nogo-A antibodies have shown promise in enhancing regeneration and recovery in animal models, leading to a large-scale clinical trial conducted by Novartis Pharma in collaboration with clinical trial networks.

Immune-Based Therapies for SCI

Immune-based interventions such as autologous activated macrophages and T-cell-based vaccination show promise in promoting recovery from SCI, with autologous macrophages demonstrating safety and efficacy in phase I clinical trials.

Combination Therapies for SCI

Combining rehabilitation, neuroprotective agents like riluzole, and regenerative approaches like Cethrin may hold the key to maximizing functional recovery after spinal cord injury.

Study Limitations

1
Conventional knock-out animals are often of limited value because of compensatory mechanisms
2
Difficulties in accurately identifying the location of the border of the lesion site when the macrophages were injected
3
The results of a single arm, uncontrolled study need to be interpreted cautiously

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