Last month researchers from the École Polytechnique Fédérale de Lausanne showed that a new neurostimulation therapy permitted three paralysed spinal cord injury patients to walk again – a notable achievement, not least since the effect persisted once the neurostimulator was switched off.
The trial used a modified version of a commercial deep brain stimulator. But GTX Medical, an EPFL spin-off, is now working on a more advanced stimulator dedicated to locomotion. There will be a long way to go and a lot to do, however, before this becomes a real commercial prospect.
“This is really spectacular, what Professor [Grégoire] Courtine and his team have done,” Sjaak Deckers, GTX’s chief executive, tells Vantage. “It is the first time that with stimulation and intensive training, after a couple of months, functionality returns even in the absence of stimulation.”
The technique is known as targeted epidural spinal stimulation (Tess). The best explanation for what is happening at a mechanistic level is that spinal neurons are somehow reorganising themselves – but this would likely take post-mortem analysis to confirm, Mr Deckers says.
PET imaging studies, however, show a clear increase in activity in the motor cortex in the brain and in the cerebellum, both of which play a crucial role in locomotion.
“The areas of the brain responsible for walking really have significantly increased activity,” Mr Deckers says.
The paddle lead that carries the electrical impulses is positioned on the spine below the lesion, so this increased brain activity would suggest that some sort of reconnection of the spinal cord has been achieved.
The stimulator used in the Swiss trial was an adapted form of a Medtronic-branded deep brain stimulator, initially designed to treat patients with Parkinson’s disease. This is a common approach for neurostimulation start-ups: Setpoint Medical used a Cyberonics-branded device in its early trials, for instance.
The next step for GTX will be more trials – again, academic-led rather than sponsored by the company – still with this modified stimulator but with a newly developed GTX paddle lead. This trial will see Tess used in patients who have not been paralysed for as long as the individuals in the first trial, whose injuries had occurred at least four years previously.
“We expect the results to be even better if the simulation can start weeks after the injury, when there is less atrophy of the muscles and the nerves,” Mr Deckers says.
Conversely this means that the technology can probably not be used in patients whose spinal cords are completely severed. Mr Deckers hints, however, that GTX might one day want to investigate different technologies for patients with complete lesions.
In parallel with the academic research, the company is developing its own system. This will comprise a tailored paddle lead, a proprietary implanted neurostimulator with dedicated features for locomotion, motion sensors to synchronise the stimulation with the patient’s walking pattern plus patient and clinician programmers. Together, this should improve the technology’s precision.
GTX is pencilling in a pivotal multicentre European trial of this in-house system for late 2020, with results possible in 2022. This study will look at a wide range of outcomes, Mr Deckers says, “to collect the right data and also to get reimbursement later on. For this reason it is important to show that the therapy is both effective and economically beneficial.”
This is the other challenge GTX faces. The technology is familiar enough – similar spinal cord stimulators have been available to treat pain for decades and are regarded as safe – but there are no commercial or payment models for a device that treats paralysis. GTX could be a pioneer in a new market.
Mr Deckers is sanguine about the technology’s reimbursement prospects, pointing out that coverage decisions are largely based on benefit to the patient in terms of quality-adjusted life years. And if GTX’s device lives up to its promise its effect on patients’ quality of life will be incalculable.
But approval and reimbursement will require clinical data, and that in turn requires money. GTX last raised cash in 2016, when it was called G-Therapeutics: a €26m ($29m) series A round, plus a further €10m loan from the Dutch government – GTX is headquartered in Eindhoven. At that point Mr Deckers told Vantage that the cash would last the company three or four years.
“Obviously that was a bit too optimistic,” he says now. “We will need more cash. There’s still enough money to finish our product development, but we’re currently having discussions with investors to expand the amount of capital we have, to be able to achieve CE mark, FDA approval and beyond.”
Investors might be wary, the potentially life-changing nature of the technology notwithstanding. Translating promising results in three patients in early, academic research into a saleable product with payers’ backing ought not to be underestimated.
This is not lost on Mr Deckers. “There is an important warning: it is still an experimental technology. It’s not a miracle,” he says. “We still have to discover how much these patients will really benefit.”