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Modulation Of Gap Junction Channels For The Treatment Of Spinal Cord Injury

Project Member(s): Gorrie, C.

Funding or Partner Organisation: Spinal Cord Injury Network (Spinal Cord Injury Network - Towards Translation)

Start year: 2014

Summary: Spinal cord injury (SCI) results in a devastating loss of mobility for the victim and as many as 80% of patients develop chronic pain. Current treatment options following SCI are limited, yet the time course for the cascade of secondary lesion events and the development of chronic pain that follows initial traumatic insult offers a significant window of opportunity for intervention. Gap junction channels have been implicated in ATP release, lesion spread and inflammation, with subsequent cyst formation limiting functional recovery after SCI, and have also been implicated in the development of chronic pain. We have developed two platforms for the regulation of gap junction channels that have shown considerable preclinical potential for SCI treatment, reducing secondary lesion events and improving behavioural outcomes. One of these, a topically applied antisense oligodeoxynucleotide gel that blocks translation of the gap junction protein connexin43, is now in phase 2B clinical trials for venous leg ulcers and diabetic ulcers. The second platform, a connexin peptidomimetic is patent protected for systemic delivery in the treatment of conditions such as stroke and cancer. The aim of this project is to complete preclinical research that will provide readiness for clinical trials aimed at reducing chronic pain and improving functional outcomes after SCI. In particular, we will develop the peptidomimetic platform for SCI in parallel with clinical advances for other indications in order to ensure rapid uptake and clinical development, or to promote off label use as soon as the drugs proceed for other larger, market driven indications.

Publications:

Mao, Y, Tonkin, RS, Nguyen, T, O'Carroll, SJ, Nicholson, LF, Green, CR, Moalem-Taylor, G & Gorrie, CA 2017, 'Systemic administration of Connexin43 mimetic peptide improves functional recovery following traumatic spinal cord injury in adult rats.', Journal of Neurotrauma, vol. 34, no. 3, pp. 707-719.
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Tonkin, RS, Mao, Y, O'Carroll, SJ, Nicholson, LF, Green, CR, Gorrie, CA & Moalem-Taylor, G 2015, 'Gap junction proteins and their role in spinal cord injury.', Frontiers in Molecular Neuroscience, vol. 7, pp. 1-9.
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Moalem-Taylor, G, Mao, Y, Tonkin, R, Nguyen, T, O'Carroll, S, Nicholson, L, Green, C & Gorrie, C 2015, 'Systemic delivery of a mimetic peptide against CONNEXIN43 GAP junction protein in rats following spinal cord injury', JOURNAL OF NEUROCHEMISTRY, 25th Biennial Meeting of the International-Society-for-Neurochemistry Jointly with the 13th Meeting of the Asian-Pacific-Society-for-Neurochemistry in Conjunction with the 35th Meeting of the Australasian-Neuroscience-Society, WILEY-BLACKWELL, Cairns, AUSTRALIA, pp. 361-361.
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Keywords: Connexin43, spinal cord injury, peptide,

FOR Codes: Cellular Nervous System, Nervous System and Disorders