Spinal cord injury therapies research overview- Update: May 2019

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This overview was set up by Corinne Jeanmaire, for the endParalysis foundation and for the ESCIF (European Spinal Cord Injury Federation) Research Group. With thanks to Sam Maddox,  Chris Powell (blog) and Harvey Sihota (Neurokinex) their input and to Beverley Saunders and Barbara Carlile for their editing support.

We have to be clear:  there is still no cure, therapy or treatment for (chronic) spinal cord injury. Judging by the increasing number of ongoing and planned clinical trials though, it seems that we might have come a bit closer to achieving a certain level of recovery.

The data displayed in the tabs in this page is far from exhaustive but is simply meant to give an idea of the momentum currently at play. We have divided up the data into four blocks, being:

1. (Stem) cells & combination regeneration/repair strategies.
2. Scar and growth inhibitors reduction & regeneration/repair combination strategies.
3. Electrical stimulation of the spinal cord (e-stim), Transcranial Stimulation (TMS), Brain-Machine-Interface (BMI), etc
4. Unproven/ commercial therapies.

Disclosure: The purpose of this section of our website is to provide a summary of the important developments in spinal cord research towards finding a cure or repair / recovery therapy. In line with the scope and focus of the endParalysis foundation, we will mainly focus on research projects currently applied or ultimately applicable to chronic spinal cord injury and on therapies that are at clinical or pre-clinical stage and thus have a potential to be applied successfully on human patients.  Furthermore, this overview constitutes in no way an endorsement from the endParalysis foundation or from her scientific committee for any specific research project, experimental therapy or clinical trial included therein.

Onderzoek naar dwarslaesie behandeling en genezing 2018

PART I 

REGENERATION/REPAIR: (STEM)-CELL THERAPIES AND COMBINATIONS

Update March 2018

These include (stem) cell transplantation therapies, possibly in combination with grow-factors or molecule to enhance nerve regrowth or strategies to neutralize the growth inhibitors factors, and bio-material scaffolds to guide nerve regrowth and other strategies encouraging neuro-plasticity i.e. the remodeling of signals of brain and spinal cord nerves.

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1-Stemcell Inc. – Pathway study – STOPPED

• Background information:  The Pathway study was designed to test the effect of adult neural stem cells (derived from fetal tissue) transplantation to chronic spinal cord injury patients with a cervical lesion. Meaningful functional recovery was reported for a few patients who were, for example, better able to use their hand after the transplant.  The outcome was promising for many quadriplegic patients.  However, the recovery pattern was not expected to meet the study “endpoint” (objectives).  Results were therefore deemed as too moderate by Stemcell Inc. to continue the study (The company was running out of cash and it would have cost another $35 million to complete the trial enrolling 52 patients in total).  We hoped that the promising Pathway study might be taken over by another company but no such news has come through so far. Stemcell Inc. pulled the plug on the trial in May 2016 and announced a merger with Microbot Medical, in another, more lucrative market in August 2016.  More info here.

• Update (January 2018): In October 2017 we learned that the Pathway study might be taken over by a Chinese group. We did however not obtain any confirmation regarding this information.

2-Neuralstem Inc. – Neural Stem Cells – RECRUITING PATIENTS

• Background information: A clinical trial started in the USA in October 2014, sponsored by the biotech company Neuralstem, primarily to check the safety of their neural stem cells (NSI-566), on chronic spinal cord injury patients.  Four patients have been treated.  In October 2015, it was reported that the stem cells implantation had been safe and well tolerated.

• Latest update (January 2018): “With safety looking good, the green light has been given to treat more patients,” Dr. Ciacci said [June 2017].  “However, to produce effectiveness, more cells will need to be transplanted”. The University of California San Diego (UCSD) has begun recruiting four more participants with complete (Asia A) chronic cervical injury (C5-C7, 1 to 2-year post injury), to continue the trial under an amended protocol.

• Patient enrollment: The trial is being conducted at the university’s Sanford Stem Cell Clinical Center.  Researchers recommend that participants in the trial live within a 500-mile radius of San Diego, due to the intensive, 60-month follow-up schedule. For more information on the Phase I Chronic SCI study, contact Ciacci’s Research Group at (619) 471-3698, nksidhu@ucsd.edu. More about the trial: on gov (NCT01772810).

3-Combination therapy:  (Stem Cells +) InVivo Scaffold – HUMAN TRIAL SUSPENDED (CHRONIC SCI) – ACUTE SCI study: temporarily HALTED)

• Background:  Nineteen patients with an acute spinal cord injury received the InVivo Neuro-Spinal Scaffold.  Besides, the biotech InVivo Therapeutics announced, end 2015, that they were going to “focus their research efforts for chronic SCI on Bioengineered Neural Trails TM.”  These are injectable combinations of biomaterials and neural stem cells (NSCs) delivered using minimally-invasive surgical instrumentation and techniques to create trails across the chronic injury site. More info here.

Unfortunately, as part of the decision to focus exclusively on INSPIRE, InVivo announced the suspension of its chronic SCI stem cell study in July 2017. As per the press release: “The company is evaluating strategic options for allowing the cell and gene therapy programs to move forward outside of the company and plans to restart the cervical study once the FDA approves a protocol that allows for enrollment in the United States.” More info here.

• Latest update (January 2018) for Aspire acute SCI study: Seven out of the 16 (43.8%) patients evaluated so far have shown a significant improvement and have been converted from ASIA A to ASIA B (i.e. from a complete to incomplete spinal cord injury).   However, the company decided to temporarily halt the enrollment for their Inspire Study as a third patient died after being enrolled, even though “the cause of death was deemed by the Principal Investigator at the site to be unrelated to the Neuro-Spinal Scaffold™ or implantation procedure”.

Read more here. In January 2018 InVivo’s press release informed “We remain in discussions with the FDA regarding the clinical path forward in support of a Humanitarian Device Exemption filing. We are working diligently to provide clarity as expeditiously as possible as we evaluate various strategic and financing options. I look forward to providing more details on our proposed randomized controlled study in the second quarter of 2018”.

• Patient enrollment (ACUTE SCI only): Be aware, this is only valid for patients at acute stage (only hours after the spinal cord injury). More info here:  NCT03105882. The enrollment has been halted as of July 2017 (see above) and is expected to restart later.
  

4-Nose Cells and Nerve Graft – Pr Raisman (UK) and Dr. Tobakow (PL)- RECRUITING

• Background information: In October 2014, in Poland, a paralyzed man was reported to have gained recovery after some of his nose nerve cells (these were actually taken from the olfactory bulb deep in his brain) were transplanted into his spinal cord and some peripheral nerve tissue from the patient’s ankle was grafted to serve as a bridge over the lesion. Expectations from this study have to be tempered since we are now talking about a single patient. However, he went from complete paraplegia to incomplete (Asia A to Asia C) and has regained considerable functions.  Here is a link to the published data.  This study was pioneered by the late Dr. Raisman (deceased 2016).

• Latest update (January 2018): Chronic SCI patients are still (since March 2016) being recruited for a new clinical trial taking place in Poland (Dr. Tobakow).  As far as we know, the clinical trial follows the same protocol as the one applied to the first patient, i.e. extraction of olfactory cells from the olfactory bulb in the patient’s brain, a transplantation into the spinal cord and a peripheral nerve graft.

• Patient enrollment: Only patients with a transected/severed spinal cord can apply for the trial.  The cord must be clear-cut, for example by a knife, not contused.  Also, the candidates for this clinical are required to spend several years in Poland as the procedure will be preceded and followed by an intensive and lengthy rehabilitation process. More info regarding enrollment is available here: https://walk-again-project.org/#/en. Moreover, another clinical trial is in preparation, in the UK, following a slightly different protocol (the source of the olfactory cells might be different) and other patient selection criteria.  There is no public update available regarding this UK trial plan but it might involve acute injuries rather than chronic ones.

5-Schwann Cells and combinations – Miami Project- RECRUITING

• Background information:  The Miami Project launched their Schwann Cell clinical trial for chronic spinal cord injury patients in February 2015.  The transplanted cells are autologous (coming from the patient himself).

• Latest status (January 2018): The Schwann cell clinical trial completed its phase 1 (to check safety) and showed that the cells were safe.  The Miami Project is now carrying out further studies combining the Schwann cells transplantation with various other therapeutic strategies such as intensive physical rehabilitation. (Currently recruiting.)  Further studies are also in preparation and might involve the combination of Schwann cells with, respectively, growth factors, antibodies and cell-support matrices.

• Patient enrollment: The study is currently recruiting patients with a chronic injury (at least one-year post injury, complete or incomplete C5-T12 injury, 18-65 years old). For details and enrollment see here: NCT02354625

6-Dr. Wise Young- Umbilical Cord Blood Stem Cells + combinations – PUBLISHED- Phase II in preparation

• Background information: In the fall of 2014, Dr. Wise Young, Rutgers University and SCINetChina, presented some preliminary information from the Umbilical Cord Blood & Lithium Phase II clinical trial that had taken place in China.  He explained that although none of the chronic ASIA A participants had improved motor scores, 15 out of the 20 patients were able to take steps with the aid of a walker whilst in rehabilitation.  You can view a part of Dr. Young’s presentation during 2014 Working2Walk symposium, here. The study has now been published in an open access journal, Cell Transplantation.  See abstract of the publication here.  A lot of questions remain as to the extent of “functional” recovery obtained (is it functional even though the motor scores of patients have not improved, meaning that they cannot contract any muscle on order?).  Also, the source of the changes shown in patients needs to be clarified (the combination of stem cell transplant with an intensive physiotherapy regimen made it difficult to identify the source of improvement).

• Latest update (January 2018): Clinical trial in the USA in preparation: To our knowledge, Dr. Wise Young is raising funds to carry out a similar clinical trial, this time in the USA, Phase IIb (aiming to prove efficacy) which will consist of three groups of nine, ASIA A, C5-T10 patients.  The first group will get umbilical cord blood stem cell injections plus six weeks of oral lithium plus intensive rehab.  The second group will get umbilical cord blood stem cells plus intensive rehab.  Group three will get intensive rehab only. A list of Questions and Answers regarding the upcoming clinical trial is available here. Information regarding the intensive walking program included in the study is published here.

• Patient Enrollment: This study is in preparation and is not recruiting patients yet.

7-Bone Marrow Stem Cells Intrathecal Injection- Dr. Vaquero Phase II clinical trial (Spain) – Phase II trial completed.

• Background info:  Vaquero (M.D. Puerta de Hierro University Hospital, Spain) has been studying the impact of the autologous (from the patient himself) bone-marrow mesenchymal stem-cells intrathecal injection (in the subarachnoid space).

• Latest Update (June 2017): A phase II of the trial has been carried out on incomplete spinal cord injury patients.  According to Vaquero, (this) cell therapy helps, above all, “people who have a healthy nervous system, but does not guarantee success in a person with a complete spinal cord injury.”  For patients with an incomplete spinal cord injury, this therapy can significantly improve sphincter control.  In fact, Dr. Vaquero has presented several cases in which people affected by an (incomplete) spinal cord injury can more effectively control incontinence and effectively improve bladder emptying.  That cell therapy also improves spasticity and sexual function […]. Source (in Spanish- article June 2017). More scientific details in the 2016 publication (complete SCI) and 2017 publication (results for incomplete SCI).

• Patient enrollment: No information available regarding plans for another trial.

8-Neuroplast (The Netherlands) – Autologous BoneMarrow-derived Stem-Cells – Clinical trial in preparation for both chronic and acute SCI

• Background info: Neuroplast is an independent company founded in 2013 and embedded in the Science Society of Brightlands Maastricht Health Campus (brightlands.com), The Netherlands.  “A pre-clinical study showed that Neuro-Cells (Neuroplast proprietary cells that are derived from the patient’s own bone marrow) did significantly improve both locomotor functions and survival in those spinal cord-lesioned rats as compared to rats treated with a placebo”.  Source:  http://www.neuroplast.com/projects.html. Neuroplast is preparing two studies that are expected to take place in Europe. The studies involve a transplantation of Neuro-Cells that are said to have a positive effect both in terms of neuro-protection and neuro-plasticity and are expected to contribute to the level of functional recovery for patients both at an acute and chronic stage of the lesion.

• Latest update (March 2018): Neuroplast is now conducting the regulatory safety study and building partnerships with various European centers that will be involved in the implementation of the trials. Europe. There will be two studies:

– A phase I trial for chronic spinal cord injury patients.  It is expected to start in 2018 and should enroll ten patients with a SCI <2 years, Asia A, Asia B or Asia C (complete or incomplete SCI). The trial will take place in The Netherlands. The safety check will last three months and the patients will be followed up for one year after that, in order to check the effectiveness of the treatment.

– A phase II/III trial for which 81 patients with a sub–acute SCI will be recruited. The study will last two years for the patients and will take place in various European countries including The Netherlands.

• Patient enrollment (Europe): Both trials are in preparation. Patients are not yet being recruited.  It is expected that the first five patients with chronic spinal cord injury will be recruited in 2018.

9-BioArctic – SC0806 (biodegradable device+ FGF1) – clinical trials approved, recruiting patients- Sweden – Slovenia

• Background info: SC0806 is a combination of a biodegradable medical device and a drug substance (FGF1) designed to support nerve regeneration across the injured area in the spinal cord. The therapy is developed by BioArctic AB, a Swedish research-based biopharma company. BioArctic has received regulatory approval in Estonia for a clinical study in patients with Complete Spinal Cord Injury. For more info: click here. BioArctic has received funding from the European Union’s Horizon 2020 Research and Innovation Program to carry out this project.

• Update (March 5^th, 2018): The product candidate is currently in an ongoing Phase 1/2 clinical trial. The first patient was treated in 2016 at Karolinska University Hospital, Sweden.

• Patient recruitment: The Estonian patients will undergo treatment with SC0806 at the Karolinska University Hospital in Stockholm, Sweden, followed by an 18-months training period in the study to enhance the patients’ motor ability in the paralyzed part of the body. The rehabilitation will initially take place in Sweden and will then continue in Estonia.

Selection criteria:
-Single spinal cord lesion injury at the neurologic level between T2-T11.
-Maximum 10 years after injury.
-Only traumatic injuries.

More info about this trial on clinicaltrials.gov: NCT 02490501. Or contact: Hans Basun, MD, +46734411798, hans.basun@bioarctic.se

 

inal Cord Injury Research, therapies, treatments, 2018

PART II

SCAR and GROWTH INHIBITORS REDUCTION & COMBINATIONS FOR REPAIR

Update: January 2018

Background information: One of the biggest issues preventing recovery after a chronic spinal cord injury is the scar that appears a few days or weeks after the injury and prevents any axon from growing away from the lesion area. One of the key scar reduction strategies involves using the Chondroitinase enzyme.

In this chapter we are also covering the therapeutic strategies that are used to neutralize growth inhibitors (often referred to as NoGo) after the spinal cord injury, and /or promote nerve growth.

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1-ReNetX Bio – NOGO TRAP (CLINICAL TRIAL IN PREPARATION)

• Background information: The ReNetX a.k.a. “NoGo-trap” technology is expected to allow neurons to naturally re-grow by blocking factors that inhibit such growth. Contrary to the previously known “Anti-NoGo” technology, it is proved, as per the ReNetX company representatives, to bind and neutralize 3 types of inhibitors and is not limited to the NoGo-inhibitor.

The intrathecal delivery of the NoGo Trap protein delivery has shown axonal growth associated with a certain recovery of function by rats. It is reported to promote nerve sprouting and synaptic plasticity, as well as, to a lesser extent, axonal regeneration. The ReNetX company is now planning a clinical trial for cervical injury patients.

• Latest update (February 2018): ReNetX Bio is planning a phase Ib – IIa clinical trial (meant to test safety and efficacy) for patients with a chronic Cervical Incomplete injury. According to the latest news from the company (press release November 2017), the trial is expected to start at the end of 2018.

 

• Enrollment: The enrollment has not started yet. The milestones known so far are: IND (Authorization to start the trial): 2018 – Trial implementation: 2018-2020

2-CHASE IT: Chondroitinase and gene therapy for chronic SCI- PRE-CLINICAL stage (no human trial yet)

• Background information: The application of a bacterial enzyme called chondroitinase, orCh’ase, has repeatedly been proven to degrade the scar, to promote growth and to improve recovery in animal experiments. Now, it’s high time we switched to human application. However, applying it to people is challenging. The goal of the project “CHASE-IT”, initiated by the International Spinal Research Trust (ISRT), is to make theCh’asetherapy ready and safe for clinical application. It relies on an international collaboration between various researchers, among others in the UK and in the Netherlands. Recent experiments, using gene therapy models to deliver the enzyme, have moved the therapy closer to human application. CHASE-IT is the first research project co-financed by the endParalysis foundation, because of its high potential and its clinical relevance for chronic SCI patients.

• Update January 2018: Chondroitinase gene therapy: research and development

Input from Spinal Research, who initiated the project: since 2014, the CHASE-IT consortium has achieved several critical milestones by working on, and overcoming, many of the issues related to creating a safe gene therapy for chondroitinase:

-The gene for chondroitinase can now be expressed in an active form in human cells
-Expression of chondroitinase in the spinal cord can now be controlled, switching it on and off using an inducible switch responsive to the antibiotic doxycycline
-Treatment gives rise to improved walking and unprecedented upper limb function in clinically-relevant spinal cord injury models

• Next translational steps: The results to date have relied on an experimental viral vector that has not been used clinically. This is one of the issues that will be addressed in the next stage of development, of which there are four parts.

-Demonstrate inducible chondroitinase gene therapy works in chronic injuries
-Transfer the inducible gene therapy machinery developed in the lentiviral vector to the more clinically-acceptable Adeno-associated viral (AAV) vector
-Eliminate any background expression of chondroitinase when system in the uninduced ‘off’ state
-Confirm chondroitinase-AAV retains comparable efficacy as chondroitinase-L

3-Other pre-clinical studies concerning scar reduction

-UK: alternative delivery method for Ch’ase. More info: here
-CANADA: alternative  delivery method for Ch’ase.
-USA: study of non-human primates.
-USA: Rose Bengal Study by Dr. A. Parr (University of Minnesota). See January 2018 publication

ure Spinal Cord Injury 

4-CRP (CSPG Reduction Peptide) possibly in combination with ISP– to reduce the scar –  Dr. Yu Shang Lee – Cleveland Clinic (PRE-CLINICAL stage

• Background information: The formation of an enduring glial scar near the injured site leads to poor nerve regrowth capacity and poor functional outcomes in chronic stages after SCI. Chondroitin sulfate proteoglycans (CSPGs) are the major components of this glial scar. The small peptide called CSPG reduction peptide (CRP) was designed by Dr. Yu Shang Lee’s lab to meet this need. The aim of the study is to replicate and hopefully confirm preliminary results which have shown that CRP has therapeutic effects on chronic SCI in rats. CRP can be applied non-invasively by subcutaneous injection. The non-invasive character of the CRP is of great interest as it would mean that the treatment, if proven effective, will, in principle, be easily applied to human patients. This could constitute a very valuable alternative to other therapies currently under development such as Ch’ase, that requires a specific and elaborate delivery method to safeguard its effectiveness as well as safety for the patient.

• Latest update (January 2018): The CRP has been tested on a small number of chronic rats in 2017. Dr. Yu Shang Lee plans to carry out additional studies on a larger number of rats with a chronic spinal cord injury to confirm the good results obtained through the preliminary testing. The study will probably include both testing of the CRP alone and testing in combination with another peptide, the ISP peptide (dr. Jerry Silver’s lab, Case Western University). The latter peptide has also proven its effectiveness in reducing the scar tissue in a rodent model, but only in acute settings.

Cure Spinal Cord Injury Research, therapies, treatments

PART III

ELECTRICAL STIMULATION/TMS AND BMI/BCI

Update: February 2018

Cure Spinal Cord Injury Rese

Background information:  E-stim (this term can refer to neuromodulation, neuro-stimulation, epidural stimulation), TMS (Transcranial Magnetic Stimulation) and BMI /BCI (Brain Machine or Computer Interface); all these technics use different protocols and produce various outcomes. However, all of them are exploring the automaticity of the spinal cord and then trying to tap into it.  As per Dr. Reggie Edgerton: “Neuro-stimulation is the process of using gentle electrical currents to stimulate the spinal cord below the point of injury, enabling nerve circuits in the spinal cord to ‘hear’ and act upon messages coming from the brain.”  Based on various studies, those techniques seem to generate light functional return as well as (maybe) some improvement of the patient’s autonomic function (but beware that this “improvement” is mostly anecdotal and has not been the subject of many scientific publications yet).

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1-Epidural Stimulation:  Dr. Harkema (University of Louisville, Kentucky)  and other centers – (RECRUITING PATIENTS)

• Background information: Back in 2014, four spinal cord injury patients received surgically implanted electrical stimulator units (an E-Stim device was placed in the patient’s back, over the lower part of the spinal cord which sends electrical impulses to activate the lumbar circuitry). This small trial has generated a huge hype in the media, and encouraged the Christopher Reeve Foundation to launch their “Big Idea” project, designed to carry out a clinical trial to implant 36 chronic SCI patient with a comparable epidural stim device.  The results for the first four patients were published in July 2015 (for more info click here).  Two patients had a motor and sensory complete injury (ASIA A) whereas two patients had a sensory incomplete injury.  After some physical training, patients were able to stand-up and take steps when the stimulator was activated.  Is this a full recovery?  Negative, it is important to understand that movement of the limbs is only possible when the stimulation device is activated and even though patients can move their legs on command, it is not substantial enough to be labeled as “really walking.”  Nevertheless, and this is the most interesting aspect of the study, these patients have all reported to have obtained some significant autonomic recovery.  That includes bowel, bladder, sexual function and temperature control.  Unfortunately, as this data was neither published nor documented, it is difficult to assess whether the outcome can be measured as merely a slight improvement or full control.

• Latest update (February 2018):  It is reported that more patients have received an epidural stimulating device as part of Dr. Harkema’s study but the outcome of those patients was not officially shared. The only recent update shared by the Big Idea program informed that the FDA had now approved the clinical trial (expected to enroll 36 patients in the USA). Also, a poster was presented at the latest Neuroscience conference (November 2017) that expanded a bit on the effect of e-stimulation on autonomic, including bowel- bladder and sexual improvements. The poster remained rather vague about the range of improvement though and conclusion read: “Spinal cord epidural stimulation, along with activity-based training, may help provide an appropriate level of excitation to the spinal cord, targeting the neural circuitry involved in urogenital and bowel function.”. More info: here.

Furthermore, in a May 2017 scientific publication Dr. Reggie Eggerton highlights that e-stim may help people with a cervical injury to improve their grasp function, but this study was conducted on rats only. Read more: here.

 

• Patient enrollment: Quite a few other trials involving an epidural stimulator transplantation are now taking place in various places (The USA and other countries). These studies are not part of the “Big Idea” project, but still recruit patients, according to www.clinicaltrial.gov.
  • Louisville (Kentucky- USA). It is not clear to us whether the clinical trial started in 2015 is currently recruiting or not).  Thirty-six patients were expected to be enrolled in total.  According to the clinical trial registry, this trial is still recruiting patients: NCT02339233.  You may also learn more by visiting the Louisville website and applying as a potential candidate for future spinal cord research at: Louisville neurosurgery form.
  • A few other trials in various locations (USA and other countries) are involving Epidural Stimulation:
    • UCLA (California, USA). This study is focused on hand function recovery after implantation of an epidural stimulator in chronic cervical injury patients.  Click here for more details: NCT02313194
    • Vanderbilt University (Nashville, Tennessee). This study is meant to measure the effect of epidural stimulation on mobility for chronic SCI patients:  Click here for details: NCT02899858
    • University of Zurich (Switzerland). This study checks the effect of Epi-Stim on bladder control.  Click here for details: NCT02165774 – – Patient recruitment status: completed.
    •  Minnesota: see details in chapter below (E-STAND study).

2-Epidural Stimulation Study in Minnesota (E-STAND Study)– RECRUITING PATIENTS 

• Background information: Back in 2016, Dr. Lee at the Mayo clinic, implanted an electric stimulator in a few patients with a complete injury (Asia A- no motor or sensory function below the lesion).  He reported unexpectedly positive results, which motivated him and his team to start a bigger study.

• Latest Update (January 2018): E-STAND (Epidural Stimulation After Neurologic Damage) is a clinical trial led by David Darrow MD, neurosurgeo in Minneapolis, MN. From the E-STAND website (https://www.estand.org):  “The trial was constructed to figure out how to choose stimulation settings that provide the largest improvement in movement. The E-STAND trial is also hoping to begin to understand how epidural spinal cord stimulation in this patient population can affect blood pressure, heart function, urinary function, and some aspects of cognitive function.”

• Patient enrollment (Minnesota – 100 patients): According to their website, the E-STAND trial has just started recruiting patients with a chronic (>1 year) injury at C6-T10 level with Asia A (complete SCI) or Asia B rating (incomplete SCI).  Please check other details and important inclusion criteria here: NCT03026816

3-Transcutaneous e-stim: RECRUITING PATIENTS

• Background information: Transcutaneous E-stimulation is more or less based on the same working principles as Epidural Stimulation.  However, transcutaneous stimulation does not require any surgery since the device works through the skin.  The treatment is thus non-invasive, which is a big advantage vs epidural stimulation, and is therefore considered as risk-free* for the patients.  In July 2015, Dr. Reggie Edgerton’s group and a private company he has formed (NeuroRecovery Technologies/NRT) reported that five men with motor complete spinal cord injuries (two to six years after the injury) improved voluntary “locomotor-like” function.  The experiments involved a transcutaneous stimulator in combination with an oral drug already approved for anxiety disorders. See the press release and video here and the scientific publication here.  It is worth noting that the so-called “locomotor-like” movements obtained through this method are not functional since they are carried out without any weight bearing.  It is, however, an impressive result given that it occurred without any surgery.  This external stimulator technology is expected to be complementary to the implanted stimulators currently tried by other groups.

(*)Risks:  it has to be stressed that one patient, however, has reported a dramatic increase of his neuropathic pain after the treatment.  There is no other such case reported to-date and this can probably be considered as an exception, albeit a painful one.

• Latest update: To our knowledge, NRT is currently still raising funds to be able to develop and carry out a clinical trial in the USA.  A few trials are ongoing.

• Patient enrollment: A few clinical studies using transcutaneous stimulation are underway or planned in the USA and in other countries:
  • University of Zurich (Switzerland). Click for details: NCT03137108
  • UCLA (USA). This study focuses on potential improvement of bladder control following transcutaneous stimulation: NCT02331979
  • Shepherd Center NIH (USA): Only recruits patients with an Incomplete SCI level T12 and above.  Click for details: NCT02340910
  • Australia: see Project Edge below.

4-Project Edge – Neuromodulation – Dr. Reggie Edgerton, Spinal Cure Australia – CLINICAL TRIAL IN PREPARATION

• Background information:  Project Edge, launched in September 2016, will see the introduction of a five-year clinical research program in neuromodulation, in partnership with the University of Technology (Sydney), Spinal Cure Australia, and Professor V. Reggie Edgerton, with support from Spinal Cord Injuries Australia.  More info here: http://www.projectedge.org.au/

• Latest update (January 2018):  Through Project Edge, the program at UTS will initially focus on the development of transcutaneous treatments, with the first experiments hoping to return hand function to quadriplegic volunteers.  Future work may involve paraplegic patients and also epidural (implanted) stimulators. The latest update (January 2018) on de Edge website indicates that “a world-class facility is currently being constructed in UTS’ Botany facility” to house Project Edge and that “funding permitting clinical experiments will commence in 2018”.

• Patient enrollment: This study is not recruiting patients yet. More info here.

5-Dr. Gregoire Courtine, EPFL Zwitserland/ GTX Medical (previously G-Therapeutics)-NL –  RECRUITING PATIENTS

• Background information: Over the past decade, Dr. Courtine’s team developed a pragmatic therapy that restored supraspinal control over refined leg movements after severe spinal cord injuries in rodents. GTX MEDICAL, previously known as G-therapeutics is a company located in The Netherlands and Switzerland. It was co-founded by Gregoire Courtine and others, including CEO Sjaak Deckers. The company is currently developing two products:  one is a fully dedicated implantable spinal cord stimulator, and the other one is an overground body weight support platform, together with rehab equipment company Motek, who will further commercialize the latter product.   By enabling nervous system rewiring, the therapy is expected to help paralyzed people walk again, especially if they have an incomplete injury.  The approach has been successfully tested on fully paralyzed animals and is progressing to human testing. Beware: the therapy is targeting patients with an incomplete spinal cord injury.

 

• Latest update (February 2018): Gregoire Courtine has recently launched a small study enrolling 8 patients with INCOMPLETE chronic spinal cord injury in Switzerland.  The study has already recruited three patients of which two have already undergone the treatment; reportedly with some “promising” results up until now.  Those results have been highlighted during recent scientific conferences but have not been published since the study is still ongoing and recruiting.  The results obtained would include the ability for a previously hemiplegic patient to move his previously paralyzed leg, even after the neuromodulation is stopped.  It should be noted that this study is being conducted with a stimulator other than the one being developed by Decker’s team, as the latter is not fully ready yet.  According to GTX Medical-therapeutics’ CEO, the specific value of this particular study and future therapy involves thespacio-temporal aspects of walking, i.e. stimulating the spinal cord in such a way that the walking movement is facilitated.

 

• Future steps:  According to Deckers, the therapy in preparation is very promising and will largely increase the chance of people with an incomplete spinal cord injury to get back on their feet.  However, quite some time is still needed until the therapy becomes available at large.  Two to three years will be needed before GTX Medical can start a large-scale clinical trial involving many more patients from 4 to 5 rehabilitation centers in Europe.  After that, a few more years will pass until the treatment is available on the market.

 

• Patient enrollment (Switzerland): This study (STIMO) is currently recruiting participants with an incomplete spinal cord injury (ASIA C or D–level T10 or higher).  Be aware: participants have to be ready and committed to going for five to six complete months of intensive therapy in Lausanne (Switzerland).  See more details and conditions here: NCT02936453

6-Transcranial Magnetic Stimulation (TMS) or Deep Cranial Stimulation – RECRUITING PATIENTS

• Background information: TMS uses electromagnetic induction to generate electrical currents in the brain and down the spinal cord.  Some recent studies by the University of Helsinki have shown that TMS could help patients acquire new voluntary movements and perform those movements for a while, even when the stimulation was turned off.

 

• Latest update (January 2018): There are several more studies underway (see below) in Cleveland, Boston and elsewhere to evaluate TMS therapy spinal cord injury and other nervous system disorders.

 

• Patient enrollment: Various trials are recruiting patients:
  • University of Miami NINDS: NCT02446210
  • Cleveland Clinic (recruiting incomplete quadriplegic patients only): NCT01539109
  • Shepherd Center (recruiting quadriplegic patients only): NCT02611375
  • Bronx VA Medical Center (recruiting quadriplegic patients only): NCT02469675
  • University of Zurich (recruiting patients with an incomplete SCI, T10 and above. The study tests the effect of deep-brain stimulation on locomotion): NCT03053791
  • University of Sao Paulo General Hospital (Brazil): recruiting incomplete SCI patients only): NCT02562001
  • University of Sao Paulo (incomplete SCI only to check sensorimotor improvement after TMS. Be aware: inpatient rehab in Paraiba, Brazil) NCT02899637

7-Brain-Machine Interface (BMI) – Dr. Miguel Nicolelis in Brazil

• Background info: We regularly hear about paralyzed people being able to move a limb “just” by using their thought, i.e. by making use of a Brain-Machine Interface.  This was also the principle behind the experiment led and published in August 2016 by Dr. Miguel Nicolelis in Brazil (see Nature publication here).Eight paralyzed patients (out of which seven people had a complete spinal cord injury) were reported to recover partial neurologic function, both sensory and motor after a full year of training using a non-invasive BMI skullcap, along with a virtual reality training method.  As per the paper:  “Following 12 months of training with this paradigm, all eight patients experienced neurological improvements in somatic sensation (pain localization, fine/crude touch, and proprioceptive sensing) in multiple dermatomes.  Patients also regained voluntary motor control in key muscles below the SCI level […].  As a result, 50% of these patients were upgraded to an incomplete paraplegia classification. […]

 

• How does it work? As per the paper, the hypothesis is the neurological recovery results from both cortical and spinal cord plasticity triggered by long-term BMI usage.Next to awakening dormant spinal cord nerve networks, the virtual training, which also includes bio-feedback, could also have helped the patient’s brain recover a previously erased representation of his lower limbs.

 

• Patients enrollment: We are not aware of the next steps of the study.  It has to be noted that the study however exciting from a scientific viewpoint, is yet limited to a laboratory experiment on a small number of patients.  Further investigation will be necessary to distinguish the impact of the heavy training from the pure BMI effects on the patient’s partial recovery, before it can be applied in “real” life.

8-BMI – STENTRODE/BIONIC SPINAL CORD – MELBOURNE, Australia

• Background information: University of Melbourne medical researchers, with financial sponsorship of, among others, DARPA (US Defense Department) have created a new minimally invasive brain-machine interface, aimed to enable people with spinal cord injuries to move limbs with the power of thought and through the use of an exoskeleton, or bionic limbs.  More info is available in in this article.The brain-machine interface consists of a minimally invasive stent-based electrode (“stentrode”) that is implanted within a blood vessel next to the brain.  The “stentrode” records brain activity and converts the acquired signals into electrical commands, which in turn lead to movement of the limbs through a mobility assist device like an exoskeleton. More info about this project: Here

 

• Latest update (January 2018): Latest input from the Melbourne group (listen to this 2017 podcast), indicated that their first human trial (probably involving 3 patients with complete paralysis from spinal cord injury) would start in 2017. However, we have not found any further progress update on this.

 

• Patient enrollment: No information available as yet.
   

9-BMI for quadriplegic patients- Dr. A-Louis Benabid- France – RECRUITING PATIENTS

• Background information:  The Grenoble-Alpes University Medical Center (France) and regulatory authorities have granted Dr. Alim-Louis Benabid approval to begin the clinical research protocol “Brain-Computer Interface and Tetraplegia” at Clinatec.  The research aims to demonstrate the feasibility of a patient suffering from tetraplegia due to spinal cord injury to control an exoskeleton’s movements over several degrees via an implant that measures cerebral cortex activity. The study will focus on five patients and recruitment is underway.  Leti, a stakeholder in this research, has designed a permanent electrocorticography implant called Wimagine®, unlike any other in the world.  When placed on the surface of the cerebral cortex, it can transmit the brain’s signals reliably for years. Source: www. Minatec.org

• Latest update (January 2018): The first quadriplegic patient recruited within the trial was operated upon on June 21st, 2017.  An announcement by A.L Benabid, MD, PhD, during the latest WSSFN Congress in Berlin. More info on the Clinatec website: here

• Patient enrollment: This trial is recruiting patients.  Be aware, candidates should be quadriplegic, aged 18-40 and fluent in French, among other criteria.  More info: NCT02550522

Cure Spinal Cord Injury Research, therapies, treatments, 2016 – 2017

PART IV-

COMMERCIAL/ UNPROVEN THERAPIES

There is currently no cure for spinal cord injury and all therapies mentioned on this page are actually experimental, i.e. without any guarantee for results and including a certain level of risk taking.

However, the so-called Unproven/Commercial Therapies, often referred to as “medical tourism or stem-cell tourism” are even more experimental as they do not follow regulatory protocols nor do they provide any sort of transparency or scientific follow-up.  These therapies are also referred to as “commercial” because patients have to pay for them, unlike a listed clinical trial for which participation is free.

We don’t want to ignore these therapies since a lot of patients do make use of them, often at a high cost, but we do want to warn readers about the absence of proven functional results, the cost, the lack of transparency and the possible risks attached to these treatments.

How to recognize an “unproven therapy”? If the therapy is not listed under any official clinical trial registry (eg. www.clinicaltrial.gov) and if you have to pay for it, there is a big chance that the so-called “therapy” be unproven and therefore not scientifically managed.  There is currently no cure for spinal cord injury, no guarantee for success and there is always a certain risk attached to any experimental therapy. Should you however strongly desire to take that risk, we would advise you to prefer  scientifically driven studies (called “clinical trials”) as mentioned in our website rather than the so-called unproven therapies advertised on the internet.