The neuroscientist changing the meaning of spinal cord injury – E&T Magazine

Grgoire Courtine and his colleagues developed an electrical stimulation treatment that restores voluntary leg mobility to people with paralysis following spinal cord injuries. This could be merely the first step towards transforming how we conceive these injuries.

In 2018, former athlete David MZee stood from his wheelchair, spoke into his smart watch, and started to walk with the support of a rollator. Several years before, he had suffered a spinal cord injury during a trampolining accident which left him paralysed from the waist down.

MZees convalescence came from decades of research, including 10 years of work on spinal cord dynamics by Professor Grgoire Courtine, a neuroscientist at the Swiss Federal Institute of Technology (EPFL) in Lausanne. Courtine who trained in mathematics and physics before transitioning to experimental medicine works on restoring function to people with paralysis following spinal cord injuries.

Even as of now, theres still no treatment for spinal cord injuries, he explained. You can go through rehabilitation, which means a robotic exoskeleton moving your leg, and sometimes there is spontaneous recovery and you can move around a little bit. But in 50 per cent of cases people are completely paralysed.

Courtine and his colleagues focused on the few centimetres of spinal cord within the lumbar region. This section, which controls walking, is left intact after the majority of spinal cord injuries. It had previously been shown that this could be reactivated with electrical stimulation; this was the starting point for the scientists.

At the beginning, we used a very simple approach; we stimulate the spinal cord, Courtine said. And through time we really understood what the structures are in the spinal cord which are recruited with the stimulation, meaning we gain a scientific understanding of the principles activated by the electrical stimulation in the spinal cord.

Rather than simply delivering a constant current, the researchers experimented with patterns of stimulation. They learned where and when to provide stimulation to enable locomotion, developing a pattern of stimulation to activate the relevant groups of leg muscles at the correct times in the step cycle. In 2012, Courtine and his colleagues administered this stimulation along with some pharmaceutical agents to paralysed rats, which were able to walk again.

This set in motion the long nightmare of moving from rats to humans.

According to Courtine, they encountered every possible challenge imaginable. In addition to the obvious engineering challenge, they wrangled with ethical committees, funding applications, recruitment, and finding a large dedicated space at Lausanne University Hospital. Courtine had always been aware that this was not a purely academic effort, and had started collaborating with neurosurgeon Jocelyn Bloch at an early stage to ensure that the treatment would work in patients. The two founded a start-up, GTX Medical (now Onward) in 2014 to develop the technology and manage the administrative side of the project.

In a crucial stepping stone between rats and humans, Courtine had to demonstrate that the treatment would work in non-human primates: The way we stimulate the human spinal cord is different to rats, its based on what we observed in monkeys, so this was a critical step to the translation to humans, he said.

This introduced many of the challenges they would encounter in human trials: a more complex central nervous system, high ethical standards, and intelligent subjects who could not be conveniently restrained, controlled, and euthanised as rats can. This was also the point at which Bloch surgically implanted the system (previously wired), meaning that it had to be medical-grade.

After a successful non-human primate trial, in 2018 they implanted the flexible electrodes in three human patients and applied the stimulation pattern.

The treatment not only allowed the unprecedented restoration of mobility in itself a scientific marvel but this activity also triggered the natural regeneration of nerve fibres. Nerves grew spontaneously, bypassing damaged tissue to carry electrical signals between the brain and spinal cord. This allowed the patients to regain control over previously paralysed muscles, even when the stimulation was switched off.

This was a surprise, Courtine said. You are able to stimulate the spinal cord in the way you reactivate this dormant site, which enables the immediate production of movement. It means you can train and generate activity.

That is a process where local activity depends on plasticity, meaning that when the system is active it triggers the growth of new connections: the reorganisation of neuronal pathways in a way that after this long period training with stimulation enables this very activity. You have the growth of new connections that enable the recovery of some function without stimulation.

After five months of training and physical therapy, all three patients were able to voluntarily control their leg muscles and walk for as long as an hour without muscle exhaustion, even leaving the laboratory and walking outdoors.Ten patients have now recovered voluntary leg mobility through this approach.

Since then, Courtine and Onward have been working towards commercialising their approach such that it can reach thousands of people. They improved the technology, replacing their previous electron array with a version better suited to facilitating movement and refining the stimulator. They realise that this technology needs to be convenient to use; they envision the user simply saying stim[ulation] on or stim[ulation] off to their smart watch to begin training.

Meanwhile, they are setting up clinical trials to try this treatment in people with fresh spinal cord injuries, as data from rats and non-human primates suggest there is a window of opportunity (with greater plasticity) following the injury. They hope to begin the two-year trial in 2022.

Courtine and his colleagues are also experimenting with applying electrical stimulation to other types of paralysis. As the recipient of the 2020 IET A F Harvey Prize, Courtine will have 350,000 to help broaden the scope of his research: The idea is to accelerate this understanding and technology to move this to a different location to target new function, in this case upper limb movement.

Over the next decade, Courtine hopes that Onward will be able to provide a range of treatments to improve the lives of people with spinal cord injuries in every way that matters to them. This transcends limb movement to include things like sexual function and bowel and bladder control. Asked whether he hopes to change how we conceive of spinal cord injuries as a life sentence of restricted function, Courtine chuckles.

Maybe thats a big statement, he said. But we are at least working towards that as a dream objective of our lives. Hopefully [that will happen] before I am constrained to retire.

Grgoire Courtine will present his work in a lecture hosted by the IET in London in spring 2021, broadcast live and followed by a Q&A session.

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The neuroscientist changing the meaning of spinal cord injury - E&T Magazine