Moving from rats to patients: swift progress for electrical simulation in treating paralysis

Sometimes the pace of medical progress takes even us by surprise. Last month a paper was published in the Lancet by a team of clinicians and scientists at the University of Louisville that we certainly were not expecting to see so soon, reporting that electrical stimulation of the lower spinal cord had restored voluntary movement in 3 patients who had previously been suffering from complete muscle paralysis following spinal cord injury.

Professor V. Reggie Edgerton, one of the authors of the Lancet paper, is a leader in this field of science, and only 3 years ago wrote a post for this blog on the years of careful animal research that led to the use of electrical stimulation to restore locomotion in rats following severing of the spinal cord. We took another look at Prof. Edgerton’s research last year when this laboratory breakthrough was followed by a clinical breakthrough. Rob Summers, a man paralysed after a road accident, 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 most recent study was a follow-up of this work, and was proceeding as expected until – as Helen Thompson in the Neuroscience Blog writes – something unexpected happened with a patient named Andrew Meas:

Seven months into training on how to stand using the implant, he tried to move his toe while the stimulation was on. “He just started trying to move his toe,” says Angeli. “He was like, ‘look it’s wiggling!’ Further testing showed that he was able to move his leg and ankle, too – indicating that voluntary signals from the brain were crossing the lesion.”

This was only the start, similar results were observed in 2 other patients, one of whom not only had complete motor paralysis like Andres Meas, but also complete sensory paralysis. And researchers were also in for another surprise, as time passed and training progressed less electrical stimulation was required to achieve voluntary movement, and one day Andrew Meas showed that he was able to move when the stimulation was turned off…something that he could never have done just a few months earlier.

So what was going on? After all, as we reported in a blog post this June similar results where voluntary movement was restored following complete motor paralysis were only seen in rats when electrical stimulation and training were combined with a serotonin and dopamine receptor agonist that is not yet approved for human use.  Prof Edgerton suggests that despite being clinically paralysed the spinal nerve connections in the human patients may not have been severed as completely as in the rats, and that the stimulation pushed the activity of damaged connections over a threshold needed for them to send information from the brain to the limbs:

There may be ‘silent’ connections that can’t be seen by current imaging techniques, and are too damaged to work by themselves, which can be boosted into crossing a threshold of activation by the stimulation.”

The clear demonstration of partial restoration of voluntary muscle control in previously paralysed patients using electrical stimulation techniques – techniques that are somewhat dated in comparison to those now being evaluated in animal studies – will, we hope, act as a spur for further investment in this extremely promising field.

Speaking of Research