Yesterday an article appeared in the New York Times describing how scientists, supported by the National Institutes of Health and the Christopher and Dana Reeve Foundation, have used electrical stimulation of the lower spinal cord to enable a man who had been completely paralyzed below chest level to stand again, and even to take steps on a treadmill. The good news has since spread around the world, being reported on the BBC, The Times of India, and Canadian TV .
While the reports have – perhaps understandably –focused on the fact that this breakthrough has for the first time enabled a man with complete paralysis to stand and take a few steps, the Lancet paper describing this work also reports “improved autonomic function in bladder, sexual and thermoregulatory activity that has been of substantial benefit to the patient”. Such improvements are important as they have a huge impact on the overall wellbeing of a paralysis victim.
In this video Professor V. Reggie Edgerton of UCLA, who lead the team that undertook this study, describes the background to this study, and how discoveries made in both animal and clinical research made it possible.
Regular readers of the Speaking of Research science blog may recognize his name, in October 2009 Prof. Edgerton wrote an article for Speaking of Research in response to media coverage of a study he and his colleagues had published on the use of implanted electrodes to restore motor function in rats whose spinal cord had been severed, allowing the rats to stand and walk again. This study in rats – which can be read in full in PubMed Central – proved that in the absence of input from the brain due to the spinal cord being severed, electrical stimulation of the caudal segments of the spinal cord could enable the nerve circuits in the lower spine to use input from sensory nerves to control movement, and led directly to the clinical breakthrough reported yesterday.
But as is almost always the case this advance did not come from only one study, many years of basic research in both animals, intitally in cats – where it was first shown that an animal can walk despite the complete transection of the spinal cord -and later in rats, provided the scientific basis for this work, as Prof. Edgerton himself wrote in 2009:
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 underlie our most recent publication.”
Only time will tell what this study will mean for the millions paralyzed by spinal injuries – breakthroughs like this are better viewed as the end of the beginning than as the beginning of the end – and much further research will be needed to evaluate and improve this technique before it can be considered for widespread clinical use.
Firstly, the electrode arrray used in this study was relatively basic, but was FDA approved for use in humans and so appropriate for this early clinical study. Prof. Joel Burdick of Caltech, an author on this weeks Lancet study, is working to improve the design of the electrode arrays and the patterns of electrical stimulation applied to the spinal cord. Improvements in the way in which the electrical stimulation is delivered should increase the effectiveness of the technique.
A possible second improvement could be the addition of drugs that activate the locomotor nerve circuts. In the 2009 rat study some animals were treated with agonists for the 5-HT2A and 5-HT1A/7 serotonin receptors – on the basis of earlier research in mice and rats – in addition to receiving electrical stimulation, and it was found that this combination was considerably more effective than electrical stimulation alone. Unfortunately the serotonin agonists used in the 2009 rat study are still experimental and not approved for human use, and so could not be used in the clinical study reported in the Lancet. Hopefully 5-HT2A and 5-HT1A/7 serotonin agonists suitable for use in humans will soon be developed and evaluated in clinical trials, perhaps this weeks result will encourage investment in such drugs.
Many avenues towards repairing spinal cord damage or restoring function are currently being studied, and it is possible that this approach might be superseded in some, or even most, cases by advances in stem cell and regenerative medicine, and of course the various brain machine interfaces that we’ve discussed earlier may prove more appropriate for some conditions and patients.
For today though, we offer Prof. Edgerton and his team our most heartfelt congratulations on an achievement that gives new hope to thousands.
Let’s also remember that this is but one of many examples of medical progress that animal rights activists would have prevented if they could have. Fortunately, they did not succeed. It is up to us – medical researchers, health professionals and supporters of science and progress – to make sure it stays that way!
Paul Browne
Speaking of Research 
It helps to look back in time as well. Much of what we learned about the intrinsic pattern locomotion generation in the spinal cord and its learning capabilities comes from work in decerebrate cats, going back all the way to Goltz F. (1869) Beiträge zur Lehre von den Functionen der Nervencentren des Frosches.