Modulation of Gap Junction Channels for the Treatment of Spinal Cord Injury

Faculty: Medicine
Spinal Cord Injury Network / Towards Translation ‐ Capacity Building Initiative

 This research grant is a trans-Tasman collaboration between Australian researchers (Dr Moalem-Taylor and Dr Gorrie) and New Zealand researchers (Prof Green, Prof Nicholson and Dr O’Carroll), and brings together experts in spinal cord injury, neuropathic pain, gap junction modulation and neurodegenerative disease.

Spinal cord injury is a major cause of morbidity and leads to significant physical, emotional and financial burdens for patients and their families. There is no known cure and current treatment options are limited. After the initial traumatic spinal cord injury a cascade of secondary tissue damage starts within hours, worsening the outcome for patients. The time course of secondary damage does however offer a potential window of opportunity for intervention.Thus,there is a great need to develop new treatments that can be used in this early time period, before the extensive spread of damage to adjacent healthy tissue occurs.  Our pioneering work has already shown that treatment with a specific compound, called Peptide5, can limit the spread of spinal cord damage when administered locally. Our aim now is to modify this treatment for intravenous delivery in the first hours after an injury providing a clinically relevant therapeutic approach.

The on-going spread of the lesion following spinal cord injury is mediated by dead or dying cells releasing neurotoxins that act on adjacent healthy cells causing them to die. This is facilitated in part through communication channels between cells, allowing small molecules to pass from cell to cell. Connexin43 is an important protein comprising these channels. Our group has developed Peptide5, which can bind to connexin43 and stop the channels opening. Peptide5 delivered directly to the surface of a spinal cord injury in an animal model reduces cell death, injury area, swelling, inflammation and scarring and improves locomotor function. It is often impractical, however, to apply topical medication to damaged spinal cord after injury, so we propose here to investigate intravenous delivery of peptide5 as a clinically relevant treatment. In this study, we will optimise administration of Peptide5 to the blood stream, test the effects of Peptide5 treatment on inflammation, swelling and damage spread, functional outcomes, and development of chronic pain in spinal cord-injured animals, and generate dose response information and administration protocols.

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