New Zealand researchers are doing ground-breaking work in healing technologies.
Professor Colin Green, photo Martin Sykes/NZH
Good communication, they say, is the key to success, whereas poor communication can lead to irrevocable harm – and as researchers at the University of Auckland have found, this also seems to hold true at a cellular level. The researchers have also found that by modifying the ways our cells communicate with each other, they can stop an injury from spreading and, in the process, unleash the inherent regenerative powers we have within us.
In the scientific world of regenerative medicine, in which stem cells tend to hog the headlines, this is paradigm-shifting research. It has also attracted considerable attention: two of the researchers’ studies have been published in top journals in the past month, an uncommon occurrence in the world of scientific research.
The work has been led by Professor Colin Green, whose team at the university’s Ophthalmology Department has focused attention on modifying cell membrane channels called connexons. When two cells come together, these channels dock, forming what is called a gap junction between the cells. On a good day, these channels help maintain the healthy environment needed for normal functioning. On a bad day, some of these open in a way that allows damaged cells to dump toxins onto neighbouring cells – spreading the load, but also the injury. That they do so is probably the result of an evolutionary trait that is no longer useful.
Green has been working in gap junctions for 30 years, which makes him something of a pioneer, given they were discovered only 50 years ago. He began looking at their role in wound healing in the late 1990s, his original theory being that if these junctions were kept open after an injury, this would result in faster healing. He was obliged to rewrite his hypothesis when his group discovered the opposite was true. They then found that if they prevented the channels being made, this reduced the inflammation and made the healing much faster.
One of the earliest beneficiaries of Green’s research was an Auckland man who suffered alkali burns to his cornea when high-pressure concrete was squirted into his eye. He had been told he could go permanently blind and there was no treatment that would help him. He was then treated on compassionate grounds with Nexagon, a novel gel that Green’s team had developed. His eye healed and both his cornea and vision were saved. Nexagon has since saved the sight of five others who suffered similar damage to their eyes.
Nexagon is in clinical trials with a US-based company Green co-founded in 2006, CoDa Therapeutics, which has so far raised US$42 million to put the gel through the trials necessary for FDA approval; it is in phase II human trials. Nexagon has also proved extremely effective at promoting healing in venous leg ulcers – five times faster than in the control group. The gel can be used on any injury where it can be applied externally.
More recently Green, in collaboration with neuroscientists at the university, has taken a treatment for external injuries and adapted it for use in the central nervous system. The result is the development of a peptide aimed at regulating the same gap junction channels, but which can be injected directly into the bloodstream. Professor Alistair Gunn, who heads the department of physiology, has led a team that has shown that the peptide dramatically reduces the damage done to the brain after perinatal ischaemia – this study has just been accepted for publication in Annals of Neurology.
Gunn’s colleague Professor Helen Danesh-Meyer, who heads the optic nerve research laboratory in the Department of Ophthalmology, has led a team that has shown that the peptides delivered via the bloodstream can rescue retinal ganglion cells, the neurons of sight, after a retinal stroke. That study will shortly appear in the highly ranked journal Brain.
The research led by Gunn and Danesh-Meyer has yet to enter human clinical trials, but the studies point to enormous potential for developing treatments for a range of diseases and injuries involving acute or sustained inflammation, including stroke, Parkinson’s, Alzheimer’s and multiple sclerosis, and conditions such as glaucoma and macular degeneration.
Who knows – this technology could prove better than stem cells. Green and his colleagues have shown they, too, can improve the body’s ability to heal itself, but by manipulating intercellular communication in a way that maintains a healthier cellular environment. Green, who comes across as an understated sort of fellow, says, “It’s cool. We think we’re onto something pretty good.”
CHOOSING A DOCTOR
Stick with the GP who owns up to his or her mistakes: those who are likely to dwell on failure are more likely to learn from it and make better decisions in the future than those inclined to linger on their successes. That’s according to a study, published in the journal PLoS One, that looked at neural activation in 35 experienced physicians as they learnt to decide between two hypothetical treatments in a series of virtual patient encounters. Those who focused more on their successes (and were therefore less likely to learn from their mistakes) tended to be more experienced.
DREAMING STRESS AWAY
During the dream phase of sleep, known as REM, our stress chemistry shuts down and the brain processes emotional experiences, taking the edge off unpleasant memories. This is a finding of a paper published in Current Biology, which points to why people with post-traumatic stress disorder, such as war veterans, suffer recurring nightmares and flashbacks: they might not be getting an effective dose of overnight therapy, allowing unpleasant memories to be easily triggered by unrelated events when they’re awake.
DIAGNOSING ADHD
Scientists may have discovered an accurate biomarker for attention deficit/hyperactivity disorder (ADHD), which is often criticised as being both over- and under-diagnosed. Researchers at the Albert Einstein College of Medicine in New York used functional fMRI to identify abnormalities in the brains of children with ADHD and found abnormal functional activity in several regions of the brain involved in the processing of visual attention information.
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