This weeks issue of the neuroscience journal Brain carries an unusual image; against a background of nerve activity traces a man lies on the ground, and as you scan down the images he lifts his right leg off the ground. For most people this might just be a simple warm-up exercise, but for Kent Stephenson it was little short of a miracle, because he has suffered complete paralysis after suffering a mid-thoracic spinal cord injury. Speaking about his experience Kent noted that “Everything’s impossible until somebody does it”, and this is a breakthrough that is possible due to animal research.

Kent was one of four patients participating in a pilot study of epidural electrical stimulation sponsored by the Christopher and Dana Reeve foundation, which is overseen by an international team comprising of Claudia Angeli and Susan J. Harkema of the University of Louisville, Yury Gerasimenko of the St. Petersburg’s Pavlov Institute and UCLA, led by V. Reggie Edgerton of UCLA.

Before the implantation of an epidural stimulator all four participants were unable to move their lower extremities, and two had also lost all sensation below the injury. This continues a study published in the Lancet in 2011 that evaluated the effects of epidural stimulation in the first participant, Rob Summers, was able to stand again thanks to electrical stimulation, which also improved his general health and quality of life by improving bladder and sexual function, and thermoregulatory activity.

The key findings reported in an open-access article “Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans” in Brain (and discussed in detail on the Christopher and Dana Reeve Foundation website) detail the impact of epidural stimulation in all four participants, including new tests conducted on Rob Summers. Surprisingly the 3 new participants were able to perform voluntary leg movements immediately following the implantation and activation of the stimulator, and the researchers to speculate that some pathways may be intact post-injury and therefore able to facilitate voluntary movements. For a pilot study this is extraordinarily encouraging, as it shows that many paraplegic patients, even those who are diagnosed as having complete motor and sensory injuries can benefit from this technique. V. Reggie Edgerton, who led this project remarked:

“This is a wake-up call for how we see motor complete spinal cord injury, We don’t have to necessarily rely on regrowth of nerves in order to regain function. The fact that we’ve observed this in four out of four people suggests that this is actually a common phenomenon in those diagnosed with complete paralysis.”

There should be no doubt that this is a medical advance that depended on animal research, indeed in a guest article on this blog in 2009 Professor Edgerton noted following the publication of a key Nature Neuroscience paper on epidural electrical stimulation in rats that led to this clinical trial:

It has been characterized as a major breakthrough in facilitating the level of recovery of locomotion following a severe spinal cord injury. This in itself implies that these findings were the result of a single experiment with rats. But the reality is that these experiments were based on 100s of other experiments by not only my laboratory, but many other scientists. All of the previous animal experiments relevant to our understanding of the control of movement, involving many different species ranging at least from fish to humans, have contributed to the evolution of the concepts that underly our most recent publication. This full range of animal species is essential for the continuing progress toward the development of interventions to recover all of those functions that are lost, following a severe spinal cord injury. Our particular publication only addressed the recovery of locomotion, but there are other severe functional losses such as bladder and bowel control and hand function among others that are in need of breakthroughs. It is certain that the concepts which led to the Nature Neuroscience publication would not have evolved at any time in the near future without these gradual and incremental experiments which formed the scientific basis of these concepts. There is no way that these concepts and the experimental results could have been predicted by any non-animal mechanism, for example, computer modeling.

In these videos from Professor Edgerton we see how years of careful animal research underpinned the development of this therapy.

Animal studies continue to be crucial to Professor Edgerton’s work, for example the use of rats in the evaluation of a new multi-electrode array for improving spinal cord epidural stimulation in order to enable more complete restoration of function. The success reported in Brain this week is only just the beginning!

So when you hear animal rights activists claiming that animal research is an outdated science remember these four young men who can move again, and the hundreds of scientists whose decades of careful studies in animal models of spinal cord injury made this breakthrough possible.

Paul Browne

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