Spinal research steps ahead for cure
A push to co-ordinate research into spinal cord injury may yield better results, writes Bianca Nogrady
SUPERMAN was one of the relatively lucky ones. The fall from a horse that crushed actor Christopher Reeve’s spinal cord may have robbed him of his ability to walk, move or even breathe without help, but he still had money, and he had support.
Unlike so many people incapacitated by spinal cord injury, Reeve was surrounded by a caring family and support, could afford the considerable expense of adapting his home and life to his new circumstances, and was also a powerful, visible campaigner for research into spinal cord injury.
It’s a far cry from the majority experience of spinal cord injury victims, most of whom are young men injured in accidents.
‘‘ These guys are devastated,’’ says orthpaedic surgeon George Owen. ‘‘ They can’t run, they can’t move, they feel their life is finished — they just hide, families dissolve around them and they go into a second-rate nursing home.’’
Owen and wife Barbara are co-founders of Step Ahead Australia, formerly the Spinal Cord Society of Australia. After years of running the organisation on a shoestring, Step Ahead last year entered into a three-year agreement with the federal Government, giving the organisation a mandate to coordinate research expertise focused on finding a cure.
Step Ahead has also entered into a partnership with the University of Melbourne and the city’s St Vincent’s Hospital to set up a dedicated spinal cord research laboratory.
There is plenty of Australian expertise to draw on. Australian researchers are investigating the use of human bone marrow stem cells, and the structural matrix of skin and spinal cord, to bridge the gap of damaged tissue.
Spinal cord injury can be caused by trauma, such as a car and sporting accident, or a pathological process such as inflammation, a spinal cord stroke or diseases such as Guillain Barre Syndrome. The common factor all these conditions have is the neurological consequences.
‘‘ It leads to various degrees of spinal cord damage, but the worst is complete disruption of nerve fibres that come from the brain making the muscles work and also from skin, bladder and so on up to the brain,’’ says Owen.
This can mean complete loss of motor control and sensory input from the rest of the body, leaving a person paralysed downwards from the point of the injury.
The Owens know full well the damage done by the condition. At 14, their son Sam broke his neck in their swimming pool.
‘‘ It was devastating because I was very familiar with it,’’ says Barbara Owen, who had worked as a nursing sister at The Austin in Melbourne. ‘‘ I couldn’t believe that I would have this injury in our backyard.’’
In desperation over the lack of support for patients with spinal cord injury, and the perceived apathy of the medical community, the Owens took matters into their own hands. ‘‘ When George and I started, it was ourselves who funded it, then Lions picked us up in the twilight zone, when we were not big enough to be taken notice of but we were getting too big for George and I to fund,’’ Barbara says.
That allowed their efforts to attract the attention of the federal Government.
One of the researchers associated with Step Ahead is Giles Plant, a leading expert in the field of spinal cord injury and head of the Reds Spinal Cord Injury laboratory at the University of Western Australia. He and his colleagues are investigating a double-barrelled approach to spinal cord repair that uses stem cells to rebuild nerve connections, and also tries to reduce the extent of the initial damage and scarring.
Stem cells are the hot favourite to achieve significant gains in spinal cord repair. Before his death in October 2004 — nearly 10 years after the horse-riding accident that confined him to a wheelchair — Christopher Reeve campaigned heavily in favour of stem cell research.
Unlike the more controversial embryonic stem cells, Plant is investigating the use of autologous adult bone marrow stem cells — stem cells taken from the patient themselves.
‘‘ The beauty of this is that it shouldn’t get rejected because it’s from the patient’s own body,’’ says Plant.
The first challenge, however, is to single out the right type of cell. ‘‘ The biggest problem we’ve got in the transplantation field is if you have a number of different cell types in the injury zone, and we don’t know what the complications are going to be long-term.’’
In this case, researchers are aiming for the bone marrow stromal stem cells — the progenitor cells for various skeletal tissue components such as bone, cartilage and fat cells. Experimental evidence so far suggests these stem cells can also be induced to differentiate into other cell types, such as neural cells. The idea is to inject the purified stem cells into the damaged site, where they promote repair of damaged nerves and perhaps encourage the formation of new connections to replace those lost. Early studies in rats have been promising.
‘‘ We’ve got a lot of very good results in terms of behavioural recovery,’’ says Plant. This recovery is measured by their ability to support their own weight and aspects of their walking patterns.
The researchers are also finding ways to encourage the body’s own repair mechanisms into action, using viruses to modify the stem cells so that they can secrete factors that are known to be preferential for repairing the spinal cord.
While stem cells are the flavour of the year in spinal cord injury research, as well as many other areas of medicine, Plant believes it’s going to take a multi-pronged approach to tackle the problem.
‘‘ We’re never going to have a one-cell wonder — a single wallop that cures all,’’ Plant says. ‘‘ We’re trying to approach from the point of view that maybe three or four different targets will be the way to go.’’
Another one of those targets is being studied by Kathy Traianedes, senior scientist at the Australian Stem Cell Centre in Melbourne. In this case, rather than introduce stem cells to regenerate a damaged area, Traianedes and colleagues are investigating the use of the biological matrix to recruit cells into the damaged area to repopulate and repair the area. The biological matrix is effectively the tissue structure in which cells live and develop: structural proteins, collagens, growth factors and other biological components; everything except the cells themselves.
Evidence suggests if all the right components are there, the matrix actively recruits stem cells, possibly from the blood supply, to repopulate the area.
‘‘ If you can take a biological matrix, remove all the cells and put it back into its functional area where it’s meant to be, theoretically the right cells would know what to do when they get there,’’ Traianedes says.
Dermal matrix in the skin is already being used to regenerate soft tissue deficits, including from burns. Other research has also found that when implanted into a different part of the body it can take on the characteristics of the matrix normally found in that new area. In her research, Traianedes is using spinal cord matrix wrapped in dermal matrix, which it is hoped will prevent scar tissue from the injury growing into the breach.
‘‘ We’re hoping to see a progression of potentially new blood vessels forming and migration of cells into the site and hopefully a linking of two ends of the transacted cord,’’ Traianedes says.
However, Plant is cautious about what all this research can achieve, arguing it is going to be very difficult for science to be able to completely restore spinal cord function.
‘‘ I don’t think we’ll get somebody completely cured,’’ he says. But a more realistic goal is to improve a person’s independence, allowing them such small but significant gains as being able to feed themselves, clothe themselves, recover bladder and bowel function and not have to rely on constant care. The long-term goal would always be to get them walking again, he says.
While this research is still in its early stages, Step Ahead’s co-founders are excited about the prospect of research such as this being given the opportunity to move into the clinical setting.
‘‘ We can do endless lab work, but if it’s not co-ordinated, that’s where it sits,’’ says Barbara Owen. ‘‘ We need a treatment as soon as possible provided it is ethical and evidenced-based, but there has to be a leap of faith from the laboratory model to the human application.’’
Mandate to move forward: George Owen and his wife Barbara are excited about the progress of spinal cord research