Success Stories

Professor Colin Green: Improving the body’s ability to heal itself

  • 27 Jun 2014

Faster wound healing with reduced scarring and improved functional outcome is a desirable health research target. Of more concern though are chronic or non-healing wounds which impose upon quality of life and have significant cost and healthcare ramifications. Venous leg ulcers in the United States alone account for two million working days a year lost and three billion dollars annually in treatment costs. Approximately 15% of diabetics will develop foot ulcers during their lifetime, and more than 2.5 million people each year in the United States develop pressure ulcers (figures for New Zealand are less robust but we are likely to have similar incidence rates). Globally, 43,000 deaths resulted from pressure ulcers in 2010. Treatment of these ulcers and related injuries, including to the eye, has remained difficult.

Direct cell-to-cell communication through structures called gap junctions, and uncontrolled opening in the cell membrane of the undocked half channels that make up gap junctions, has been shown to lead to wound lesion spread, inflammation and scarring. Professor Green and his team at the University of Auckland, working with colleagues at University College London, developed a gel containing short single stranded antisense DNA to transiently down regulate the expression of the gap junction protein in wounds. It has been shown in multiple models that this reduces lesion spread, reduces swelling and inflammation and can double the rate of healing. In particular, it triggers healing in wounds that have otherwise stalled. The first human to be treated with this technology was an Auckland patient with a severe chemical burn to the eye which was not healing. A single treatment with the drug triggered healing and saved the man’s sight. The research led to the establishment of CoDaTherapeutics (NZ) Ltd and subsequently CoDa Therapeutics, Inc. in the United States. The company has now successfully completed phase two clinical trials for both venous and diabetic leg ulcers and the drug has possible application in many wound healing areas.

Vessel leak R9 1

Astrocytes in the retina labelled for GFAP are seen to wrap around two blood capillaries on the left. The retina was made ischaemic for one hour and this image taken four hours later shows an area of astrocytosis (a sign of inflammation) correlating with gap junction hemichannel mediated vascular leak.

Professor Green and colleagues then set out to develop a second blocker which could be delivered through the blood stream in order to treat internal lesions such as spinal cord injury and stroke. This channel regulator is a peptide that also targets a common sign of injury and inflammation; gap junction channel mediated vascular haemorrhage. Because of this, it has potential to alleviate several chronic inflammatory diseases such as age related macular degeneration, diabetic retinopathy, arthritis and neurodegenerative diseases such as Alzheimer’s and Parkinson’s which all share a microvascular dropout component. This second blocker has so far proven to be effective in retinal stroke (effectively a two dimensional form of brain stroke), perinatal ischaemia and spinal cord injury models.

Q1. Please can you tell us a bit about yourself and how you came to be in this area of research?

I did my PhD at the University of Auckland and then worked overseas for twelve years in France, England and the United States. During that time I was in London for more than eight years, the last seven as a Royal Society University Research Fellow and Reader at University College London. My research there focused on cardiac gap junctions and developmental biology. I returned to Auckland in 1993 and in parallel with cardiac research developed the antisense approach to study gap junction roles in limb patterning. Fortuitously I had a student who insisted on working on the brain and we tested the hypothesis that blocking gap junction channels would make a lesion worse. The result was the opposite and it was downhill from there. At that time I was in Anatomy with Radiology and in 2005 I moved to Ophthalmology. We still do a lot of work on the central nervous system, especially spinal cord and in the retina of course, but the drug development was primarily on surface wounds to the skin and cornea of the eye.

Q2. How has AMRF funding allowed your research to evolve or progress to the next stage?

AMRF funding played a crucial role in the establishment of my research laboratory upon returning to Auckland. I was able to bring some equipment from London with me, but getting a new laboratory up and running is a big task. My first AMRF grant in 1993 was to continue my cardiac gap junction work. That grant was instrumental in provisioning the laboratory and in establishing a research team in Auckland. At that time I was Director of the newly established Biomedical Imaging Research Unit which also had AMRF funding towards the purchase of Auckland University’s first confocal laser scanning microscope. That instrument was incredibly important in the research of many university and external groups. In 2004 we obtained an AMRF grant to look at scar formation in the skin, and in 2006 an AMRF grant to use the antisense approach for glaucoma flap surgery. The AMRF funded research led not only to high impact publications but also seeded projects that went on to attract other funding and support, and ultimately to the translational research pathway and novel drug developments.

Q3. Please can you tell us a bit about how your research outcomes are being used in New Zealand, and the benefit to New Zealanders from your research:


Since returning to Auckland my research has supported over 50 postgraduate students, almost all of whom have gone on to develop their own careers academically or in business. Several have completed medicine or become clinical specialists (particularly in Ophthalmology). With the drug development we were able to treat (and heal) five non healing eye burns in New Zealand before the drug entered full clinical trials, with New Zealander the primary clinical site for CoDa Therapeutics first five trials. The company employs most of its staff in New Zealand, providing not only jobs, but further expanding New Zealand’s capability and expertise in drug development. CoDa Therapeutics Inc. bought in $90M of international investment whilst I was on the Board of Directors with a good proportion of that spent in New Zealand. New Zealand retains some intellectual property rights.

Longer term our research base continues to grow and over the last ten years a move towards more outcome focused research has become more acceptable. Our own research has revealed three further translational opportunities and we are working with Auckland UniServices Ltd on those. These have potential to provide further economic opportunities for New Zealand, but more importantly, improvements in health care for all New Zealanders.

Q4. Have there been significant overseas breakthroughs or collaborations resulting from your research? Please can you describe your team’s contribution to the global research effort in your area:

We have international research collaborations in the United States, Australia, Scandinavia, China, South America and Europe, and our work has raised awareness of gap junction roles in many wound healing and disease processes. Three other companies in France, Denmark and the United States have followed and complement CoDa’s approach to gap junction channel regulation. In the past 5 years we have published 45 full research papers and book chapters, and in the past two years I have been a keynote speaker at conferences in Australia, Singapore, Chile, Belgium, China and the United States. My collaborators and team members have also presented our work throughout the world.

Q5. What is the next step in your research plan?

CRG Dec2010

We will continue to research gap junction channel roles in perinatal ischaemia and infection, for diseases of the eye such as glaucoma, age related macular degeneration and diabetic retinopathy, and central nervous system injury, in particular spinal cord injury. The most exciting new area arises from analysis of our acute and chronic wound models which has led us to hypothesise that in cancer it may not be growth of new vessels that promotes tumour expansion as has been the conventional belief for the past 40 years, but rather vascular haemorrhage and disruption as a result of the inflammatory tumour environment into which vessels are growing. Protection of blood flow should reduce tumour hypoxia, promote survival of normal cells, enable the body’s immune system to better respond to the tumour, enable improved delivery of cytotoxic drugs or anti-tumour cells, and increase the effectiveness of radiation therapy. This work has attracted Return on Science funding and enabled new collaborations with Cancer Research and colleagues in Melbourne. The initial results are most encouraging.

Q6. What is your greatest hope or dream for research in this field?

To see a New Zealand discovered drug go from the basic research stage to treatment of disease. In our case, the opportunity to improve the lives of so many is a very significant driver. The pleasure in seeing something arising from basic research in your own laboratory being used to save a person’s sight as we have done is indescribable. To see such a drug available for all, with its multiple indications from leg ulcers to persistent epithelial defects in the eye, is my dream.

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