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Characterisation of Peptide5 systemic administration for treating traumatic spinal cord injured rats

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Abstract

Systemic administration of a Connexin43 mimetic peptide, Peptide5, has been shown to reduce secondary tissue damage and improve functional recovery after spinal cord injury (SCI). This study investigated safety measures and potential off-target effects of Peptide5 systemic administration. Rats were subjected to a mild contusion SCI using the New York University impactor. One cohort was injected intraperitoneally with a single dose of fluorescently labelled Peptide5 and euthanised at 2 or 4 h post-injury for peptide distribution analysis. A second cohort received intraperitoneal injections of Peptide5 or a scrambled peptide and was culled at 8 or 24 h post-injury for the analysis of connexin proteins and systemic cytokine profile. We found that Peptide5 did not cross the blood-spinal cord barrier in control animals, but reached the lesion area in the spinal cord-injured animals without entering non-injured tissue. There was no evidence that the systemic administration of Peptide5 modulates Connexin43 protein expression or hemichannel closure in the heart and lung tissue of SCI animals. The expression levels of other major connexin proteins including Connexin30 in astrocytes, Connexin36 in neurons and Connexin47 in oligodendrocytes were also unaltered by systemic delivery of Peptide5 in either the injured or non-injured spinal cords. In addition, systemic delivery of Peptide5 had no significant effect on the plasma levels of cytokines, chemokines or growth factors. These data indicate that the systemic delivery of Peptide5 is unlikely to cause any off-target or adverse effects and may thus be a safe treatment option for traumatic SCI.

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Acknowledgements

This work was supported by the Australasian Spinal Cord Injury Network and the CatWalk Spinal Cord Injury Trust New Zealand. YM was supported by a University of Technology Sydney Doctoral Scholarship and an Australian Government Research Training Program Scholarship.

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Authors and Affiliations

  1. Neural Injury Research Unit, School of Life Sciences, Faculty of Science, University of Technology Sydney, P.O. Box 123, Broadway, NSW, 2007, Australia

    Yilin Mao, Tara Nguyen, Caitlyn Warren & Catherine A. Gorrie

  2. Neuropathic Pain Research Group, Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia

    Ryan S. Tonkin, Justin G. Lees & Gila Moalem-Taylor

  3. Department of Anatomy and Medical Imaging and The Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, 1142, New Zealand

    Simon J. O’Carroll & Louise F. B. Nicholson

  4. Department of Ophthalmology and The New Zealand National Eye Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, 1142, New Zealand

    Colin R. Green

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  1. Yilin Mao
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  2. Tara Nguyen
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Contributions

Prof. Colin Green is a founding scientist of CoDa Therapeutics, Inc. (USA) and OcuNexus, Inc. (USA) which hold intellectual property rights related to Peptide5. For the remaining authors, no competing financial interests exist.

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Correspondence to Catherine A. Gorrie.

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Mao, Y., Nguyen, T., Tonkin, R.S. et al. Characterisation of Peptide5 systemic administration for treating traumatic spinal cord injured rats. Exp Brain Res 235, 3033–3048 (2017). https://doi.org/10.1007/s00221-017-5023-3

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