Clinical Trials Targeting Secondary Damage after Traumatic Spinal Cord Injury

Abstract

Spinal cord injury (SCI) often causes loss of sensory and motor function resulting in a significant reduction in quality of life for patients. Currently, no therapies are available that can repair spinal cord tissue. After the primary SCI, an acute inflammatory response induces further tissue damage in a process known as secondary injury. Targeting secondary injury to prevent additional tissue damage during the acute and subacute phases of SCI represents a promising strategy to improve patient outcomes. Here, we review clinical trials of neuroprotective therapeutics expected to mitigate secondary injury, focusing primarily on those in the last decade. The strategies discussed are broadly categorized as acute-phase procedural/surgical interventions, systemically delivered pharmacological agents, and cell-based therapies. In addition, we summarize the potential for combinatorial therapies and considerations.

Keywords: acute and sub-acute strategies; biomaterials; neuroprotective therapies; spinal cord injury repair.

Figure 1

(A) Axial cross section of spinal cord surrounded by the boney spinal column. (B) Coronal cross section of spinal cord and column showing the different meningeal layers that protect the spinal tissues.

Figure 2

(A) Components of the BSCB, in which the neural blood vessel is composed of endothelial cells surrounded by pericytes and end feet of astrocytes that tightly regulate entry of drugs, solutes, and cells into the CNS. (B) Components of the secondary injury response, in which a compromised BSCB results in entry of peripheral immune cells, recruitment of microglia, reactive astrocytes, OPCs, and fibroblasts, and fibrotic scar deposition.

Figure 3

General categories of approaches to treating an SCI discussed in this review.

Figure 4

Intact cervical and thoracic spinal cord tissue can float freely within the spinal column in humans. Top panel—T2-weighed sagittal and cross-sectional images of the cervical spine. Bottom panel—T2-weighed sagittal and cross-sectional images of the thoracic spine. Dark structures where the red arrows are pointing are the spinal cord tissue and the lighter areas depict cerebral spinal fluid-filled subarachnoid space. Images are courtesy of Dr. Tobias Prasse.