Picture: EPFL – Switzerland

Written by Corinne Jeanmaire – Edited by Beverley Saunders, December 2018.

E-stimulation helps patients with incomplete spinal injury walk again

Recent news (again) reported a breakthrough study in the field of spinal cord injury research with many headlines reading “three paralyzed people walk again…”

As usual, nothing is that simple. The headline should actually have highlighted two important aspects: firstly, these people had an incomplete spinal cord injury and, although not able to walk much or at all, they were already able to move and/or feel their body below the level of their injury before the treatment. Secondly, the treatment is very far from a cure for paralysis: while both patients continue to improve, they still use wheelchairs in their daily lives.

To avoid any misunderstanding, some basic data regarding this study is described here. We also asked Mr. Sjaak Deckers, CEO of GTX Medical, to answer a few key questions. GTX medical is a start-up company founded by Gregoire Courtine (EPFL, Switzerland), the main author of the publication, neurosurgeon Prof Jocelyne Bloch (CHUV, Switzerland), CEO Sjaak Deckers, and several co-workers, with the aim to develop the devices needed for this therapy towards an approved product and make it a new standard of care for people with a spinal cord injury.

A. Key data about the patients before and after the treatment

Source: Extracted from scientific publication – Nature: http://www.nature.com/articles/s41586-018-0649-2

Subjects’ neurological status according to the International Standards for Neurological Classification of Spinal Cord Injury at study entry and after completion of the five-month training program.

*Reason for AIS C classification in spite of motor scores of 0 throughout all lower extremity key muscles is the presence of voluntary anal contraction.

B. Key information about the study

What did the treatment involve for the patient?

• A surgical procedure called laminectomy, during which a paddle electrode array attached to a lead is surgically implanted. This paddle electrode array will then be connected to a neurostimulator that is implanted subcutaneously in the abdominal cavity.
• Intense walking training for 5 months
  

  E-stimulation helps patients with incomplete spinal injury walk again

What is Targeted Epidural Spinal Stimulation (TESS): In the case of an incomplete spinal cord injury a part of the nerve fibers of their spinal cord were spared. TESS is specially designed to deliver electrical stimulation bursts targeting individual posterior roots of the spinal cord to amplify the residual commands from the brain, enabling voluntary control over specific leg muscles in individuals with severe but incomplete spinal cord injury. Combined with an intensive rehabilitation program, this enables voluntary control of paralyzed leg muscles.

How does this particular system work: (source: https://courtine-lab.epfl.ch)

C. Q&A to Sjaak Deckers – CEO of GTX medical B.V.

1- A really exciting part of the recent publication is the fact that some of the patients could still make the same movement that was set-up even after the stimulator was turned OFF (https://youtu.be/G5rs-78-hBo). Dr. Courtine has interpreted this fact as neurological repair (read in various news media). However, a few reports stated that findings and recordings made by alternative studies conducted by other groups (sometimes using other devices) revealed that effects were only temporary and sustainable for a few weeks after the last e-stimulation process. Is it clear, in this study, how long the function recovery sustains after the stimulator is switched off?

As far as we know, Courtine is the first to demonstrate lasting functional recovery without stimulation after intensive rehabilitation training with TESS (Targeted Epidural Spinal Stimulation). There are some studies with non-invasive stimulation that have shown some improved function for several weeks but never as convincingly as with Courtine. This new functionality (such as standing and sitting down, standing upright, traveling short distances, possibly recovery of other body functions) is in principle permanent, as long as the patient keeps exercising. As with all other bodily functions, the strength and intensity will decrease when the function is not used. We may expect that neuroplasticity (neurological adaptability) in patients with a more recent spinal cord injury will be greater than in chronic patients and that we can achieve even more in these patients.

2- Was any improvement or recovery measured regarding bladder, bowel and sexual function in the recently published study? If so, what was this improvement? Are we speaking of a slight improvement that might be associated with the increased physical activity or can we expect a real recovery of those functions, which would mean that the patient does have real control of those functions, i.e. sensation and no leakage anymore?

The clinical endpoints of the STIMO-study are focused on improving motor function. Recently, an American research group reported a promising positive effect of continuous epidural electrical stimulation on voiding in patients with a chronic complete SCI (link to publication: Herrity et al. 2018). These types of improvements can very well be a result of increased mobility and activity and the stimulation and need to be further investigated.

3-The publication includes a table of measurements before and after the treatment (e.g. Lower extremity motor score, Light Touch Sensory Scores). Is the measure “After” carried out when the stimulator is on or off?

All measurements in the table, both before and after, were performed without stimulation; otherwise, it would not have been a fair comparison.

4- Did some of the patients have neuropathic pain before the study and do we know if their neuropathic pain level was affected by e-stim, one way or another?

So far, no major effects of stimulation on neuropathic pain have been reported.

5- The publication focuses on three particular patients. The clinical trial for which those three patients were recruited did originally include 8 patients. Have other patients been treated besides those particular three and what were the results for them? The clinical trial still recruits patients, according to www.clinicaltrials.gov. Can you confirm how many patients are still needed?

At the time of writing, five patients were included. Courtine has reported on a homogeneous group of three patients with cervical trauma and who are participating in the study extension. The other two patients had a thoracic trauma. One of these two patients already had severe neuropathic pain and could not keep up with the training program; the other patient ended his participation for personal reasons at the end of the main study, despite successful treatment with good functional outcomes. Psychological assessment and good communication about the expected effects of the therapy have been crucial. Meanwhile more implants have happened, and patients are now in the training phase.

6- The video indicates that the next trial will involve patients with a much more recent injury (one-month-old or less). At this stage (1-month post-injury), the level of spontaneous recovery after a spinal cord injury is still quite high. How is this integrated into the study and how is it going to be proved that the improvement is really due to the therapy rather than a natural (partial)recovery? Is this trial going to be taking place in Switzerland or elsewhere? How many people are going to be recruited? Are these going to be ASIA C and ASIA D lesion only?

The first study was carried out with chronic patients to avoid confusion with spontaneous recovery. Two independent studies have recently been published with prediction models in which measurements after 2 and 4 weeks can predict as to what the expected recovery can be, i.e. whether someone will be able to walk again or not. We will use these statistical prediction models to show that our therapy can improve the recovery in people with a poor prognosis. Courtine is starting to prepare for such an academic study. Depending on funding, this study is planned to take place in some clinics also outside of Switzerland.

7- So far, in the study, a Medtronic stimulator is used. GTX medical is developing their own stimulator. When do you expect it to be ready? Is it going to be used for the next trial? What is the main hurdle to get it to the clinics? Is it technical, financial, regulatory?

GTX medical is developing a neurostimulation system, which will be evaluated in a comprehensive clinical study to obtain CE marking, starting in a few years from now. In that study, we will also collect more data to qualify for reimbursement from health insurance companies.

8- Is the longer term and larger scale trial going to be focused only on an early injury like the upcoming study or is it going to include patients with an “old” injury?

When our system is completely ready, we will indeed start an international multi-center trial for approval on the European market. We now assume that both people with early and chronic injuries can participate in that study.

9- We, spinal cord injury patients, receive a lot of commercial promos inviting us to get an e-stimulator implant in some exotic country like Thailand or China. The price is not included in the advertisement; it certainly is anything but cheap. What would you say to people who are frustrated that getting new therapies to the market takes so long time and who are tempted to raise the funds from their friends and family to get the treatment overseas?

The therapy offered in Thailand (Epidural Stimulation Now) is an old therapy that was introduced by Dr. Edgerton and Dr. Harkema more than 10 years ago, with only a few patients. They use a standard INS and a standard probe that have not been developed for walking in paraplegic patients but for chronic pain. The probe is actually short and narrow, which may prevent the right nerves from being stimulated. The INS cannot control various (flexor and extensor) muscle groups alternately left and right, which is essential to support walking properly. We cannot provide further advice on this treatment. As described above, we will start the clinical evaluation of our Go-2 system within the foreseeable future, for which we will of course also recruit patients. In an intensive collaboration with the Courtine group, this system is specially designed to allow people with paraplegia to stand, walk, and to make other movements possible. This may also improve various other bodily functions and may reduce problems such as bedsores.