Western Australia’s Neurotrauma Research Program (NRP) was the first neurotrauma research initiative to receive State-based funding. NRP Executive Officer Louise Goodes describes the program’s assault on spinal cord injury …

Together our scientists are tackling each vital aspect of the spinal cord injury puzzle – from nursing nerve cells through trauma, to stimulating and guiding neural re-growth, right through to driving physical and psychological recovery via innovative methods of exercise and rehabilitation.  

Keeping cells alive

Immediately after a spinal cord injury, a cascade of biochemical reactions begins, leading to further (secondary) nerve damage.  Professor Sarah Dunlop and Dr Melinda Fitzgerald at The University of Western Australia (UWA) are studying an anti-glaucoma drug, “lomerizine” (a calcium channel blocker) which they have shown to be effective in reducing this collateral damage. 

It is now clear that lomerizine can reduce morphological disruption and oxidative stress, protecting retinal ganglion cells from secondary death. However, because the drug does not prevent axonal demyelination, it will be necessary to combine the treatment with other therapeutic agents in order to preserve function in the long term.

Regenerating nerve tissue

The NRP is funding several projects aimed at stimulating the re-growth of spinal cord tissue. 

Dr Giles Plant (UWA) continues his research into olfactory ensheathing cells (OECs), which have been shown to have a positive effect in the repair of the spinal cord. Following a successful OEC transplant, you would ideally see re-growth of the injured long nerve fibres as well as the restoration of their myelin sheaths (insulation) so they can work efficiently. Teaming up with Professor Alan Harvey (UWA), the current project looks at the capacity of OECs to produce myelin and the mechanisms involved.  The findings will help toward the development of protocols to select and grow OECs to best carry out specific repair functions in the spinal cord.

Dr Plant and Dr Stuart Hodgetts at UWA (in collaboration with Dr Paul Simmons, the Brown Foundation, University of Texas) are working on two initiatives involving transplantation of purified human bone marrow stromal cells, which as they have already demonstrated, results in functional improvement in rat. 

Their first project is based on a contusion injury model – the cord is bruised and a cyst or ‘syrinx’ forms, as is so often the case following spinal trauma. Experiments are underway to ascertain the mechanisms of repair following the cell transplantation – whether it is down to the endogenous stem cells or via a process of re-myelination.

The second study involves a complete transection model of spinal cord injury and looks at the effect of combining the anti-scarring agent “decorin” with bone marrow stromal cells. 

Doing no harm

Although considerable re-growth will be needed for sprouting fibres to reconnect the brain to the rest of the body, NRP scientists are mindful to ensure regenerative technologies never make a bad situation worse. It is important to control growth so it doesn’t occur at the expense of accuracy and won’t lead to the formation of tumours.  

Gene therapy is a method being used globally to increase the viability and regenerative capacity of injured nerve cells in the spinal cord.  It involves the use of modified viruses to introduce neuro-protective and/or growth-promoting genes into cells.  Professor Harvey, Professor Don Robertson and Dr Kathy Heel (all at UWA) are examining the effects of long-term introduction of growth-promoting genes.  Results so far indicate that such treatment does indeed cause changes in the dendritic architecture of nerve cells – changes that vary depending on the type of transgene introduced. 

While gene therapy may eventually be of benefit to spinal cord injury patients, this work has important implications and highlights the need for exhaustive basic research before proceeding to human clinical trial with any new strategy.

Driving recovery through activity

Specific and meaningful physical activity is another essential aspect of recovering function after spinal cord injury.

“Our experiments have shown that neuro-regeneration must go hand in hand with intensive practice. Movement and exercise is vital to guide re-growing nerve fibres in the right direction and build robust connections,” says Professor Sarah Dunlop, who is based at UWA and heads the NRP-funded Move Again Program (MAP).

MAP investigators (a large, multidisciplinary group from several institutes and the Sir George Bedbrook Spinal Injury Unit) are in the process of developing and testing exercise programs for rehabilitation and recovery in individuals with spinal cord injury.

Associate Professor Gary Thickbroom (UWA), in collaboration with Professor Frank Mastaglia (Centre for Neuromuscular and Neurological Disorders) and Dr Dylan Edwards (Burke Medical Research Institute, New York), is studying Transcranial Magnetic Stimulation – both as an assessment tool and as an intervention to facilitate neural activity and thereby help people regain useful movement.  

Supporting emotional and psycho-social recovery

The NRP also recognises the importance of an individual’s emotional and psychological wellbeing during life’s journey following spinal cord injury.  Professor Stephan Schug, Dr Michelle Byrnes and other investigators at Perth’s Sir George Bedbrook Spinal Unit are helping to facilitate useful changes in the way spinal cord injury patients who experience chronic pain are managed and assisted, including via an ongoing holistic Lifestyle, Education and Activation Program (LEAP).

An innovative new program known as Mindfulness-based cognitive therapy, aimed at helping groups of individuals cope with the extraordinary levels of adjustment required following spinal cord injury, is also being examined by Dr Byrnes, Dr Janet Beilby (Curtin University of Technology) and Dr David Blacker (Sir Charles Gairdner Hospital).

It will take all this and more

The NRP continues to expand and deliver exciting research findings that provide hope for those whose lives are impacted by spinal cord injury. Final results of the research described above will be published late in 2010 and during 2011. 

Of course each initiative, as well as research that is being conducted elsewhere throughout the world, will generate further questions. There is obviously still a long way to go before curing spinal cord injury becomes a reality. 

The NRP remains committed to the journey – to forging bravely ahead – to getting there via incremental steps.

For information on the NRP, please visit the website: www.nrp.org.au or contact Louise Goodes on 041 891 1878 or via lgoodes@waimr.uwa.edu.au