Wednesday, June 27, 2012

Paralysed Rats Walk!


'Hope' for the paralysed?

Paralysed rat walking Paralysed rat in harness walking after chemical-electrical stimulation

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Seven years ago I stood on a bridge over the M40 doing a "piece to camera" for a report about spinal repair. The aim was to come up with a metaphor for how researchers at University College London were trying to overcome spinal cord paralysis.

It went something like this: "Imagine your spinal cord as a motorway, the cars travelling up and down are the nerve fibres carrying messages from your brain to all parts of the body. If this gets damaged the cars can't travel. The messages are blocked, the patient is paralysed.

"Normally there is no way of repairing a severed spinal cord. But the team at UCL took nasal stem cells, and implanted them into the area of damage. These formed a bridge, along which the nerve fibres re-grew and re-connected."
 
The research at the Spinal Repair Unit at UCL involved rats, not humans. In my TV report we showed rats unable to climb a metal ladder after one of their front paws had been paralysed to mimic a spinal cord injury. But after an injection of stem cells, the rats were able to move nearly as well as uninjured animals.
"Difficult and complex" The hope then - and now - is that such animal experiments will translate into similar breakthroughs with patients. Seven years on and the team at UCL led by Professor Geoff Raisman are still working on translating this into a proven therapy for patients. He told me "This is difficult and complex work and we want to ensure we get things right."

So it was with a sense of caution that I approached some Swiss research in the latest edition of the journal Science in which paralysed rats were able to walk again after a combination of electrical-chemical stimulation and rehabilitation training.

The research prompted some newspaper reports talking of "new hope" for paralysed patients. The lead researcher, Professor Gregoire Courtine enthused: "This is the World-Cup of neurorehabilitation. Our rats have become athletes when just weeks before they were completely paralysed."

My colleague James Gallagher has reported on the research and you can read his copy here.

A brief summary of the research is this: the team at the Federal Institute of Technology (EPFL) in Lausanne injected chemicals into the paralysed rats aimed at stimulating neurons that control lower body movement. Shortly after the injection their spinal cords were stimulated with electrodes.

The rats were placed in a harness on a treadmill which gave them the impression of having a working spinal column and they were encouraged to walk towards the end of a platform where a chocolate reward was waiting. Over time the animals learned to walk and even run again.

Prof Courtine, who holds the International Paraplegic Foundation Chair in Spinal Cord Repair at EPFL said: "After a couple of weeks of neurorehabilitation with a combination of a robotic harness and electrical-chemical stimulation, our rats are not only voluntarily initiating a walking gait, but they are soon sprinting, climbing up stairs and avoiding obstacles when stimulated."

The major question is this: What does this mean for humans who are paralysed?

"Ground-breaking" Prof Courtine said he was optimistic patient trials would begin in "a year or two" at Balgrist University Hospital Spinal Cord Injury Centre in Zurich.

Other scientists gave a mixed response to the findings. Dr Elizabeth Bradbury, Medical Research Council Senior Fellow, King's College London, described the Swiss experiments as "elegant" and "ground-breaking". But she said questions remained before its usefulness in humans could be determined.

She said: "Firstly, will this approach work in contusion/compression type injuries? These injuries involve blunt trauma, bruising and compression of the spinal cord and are the most common form of human spinal cord injury. Very few human spinal cord injuries occur as a result of a direct cut through spinal tissue (as was the injury model in the Courtine study).

"Secondly, will this technique work in chronic (long-term) spinal injuries? It is not yet known whether it is possible to generate extensive neuroplasticity in a system that has been injured for a long time and now contains many more complications such as abundant scar tissue, large holes in the spinal cord and where many spinal nerve cells and long range nerve fibres have died or degenerated."
 
That term "neuroplasticity" is crucial. It refers to the ability of the brain and spinal cord to adapt and recover from moderate injury - something which researchers have been trying to exploits for years.
Prof Raisman of UCL said few people, even doctors, were aware that around half of all patients who become paralysed will walk again no matter what treatment they have. He questioned whether the improvements in the paralysed rats might in part be due to spontaneous recovery - neuroplasticity - rather than the combination of interventions.

Prof Raisman is now conducting trials with paralysed patients in Poland, who are all at least 18 months post-injury which removes any doubt that spontaneous repair may be the cause of any improvement.

False hope Other scientists are scathing about efforts to repair the spinal cord. Dr Jan Gawronski, consultant in rehabilitation medicine, Royal National Orthopaedic Hospital, said the Courtine study was "yet another example of research that would lead nowhere". He said scientists had been doing rat studies on neuroregeneration for decades and "not one had led to a breakthrough for patients."

He pointed me to a recent article in the journal Spinal Cord, by neurologist Dr L S Illis in which he states: "There is not a single example of experimental work translating into a therapeutic effect. ...It would be difficult to find any other branch of science with over a century of such sterile endeavour."

Supporters of this field of research would counter with the case of Rob Summers, a paralysed American patient who is now able to stand with electrical stimulation of his spinal cord. We reported on his case last year, which appeared in the Lancet journal. He could walk on a treadmill while being supported. But doctors warned that the research was still very much at the early experimental stages.

There are research teams worldwide trying to find ways of curing spinal cord injuries.

But until there are successful trials involving several patients, scientists and journalists need to be careful about giving false hope to patients living with paralysis.
If you want to see a video release of the Swiss research then you should click on the box below. I should warn you that it shows experiments with rats in a harness walking on a platform while their spinal cord is being stimulated.
Footage of rat being retrained to walk using robotic harness (courtesy of Swiss Federal Institute of Technology)


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