Cure Spinal Cord injury latest therapies Research, treatments

Spinal cord injury therapies research overview

Update: June 20, 2019

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 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.

Cure Spinal Cord Injury Therapies Research, treatments, 2019

Cure Spinal Cord Injury Therapies Research, treatments, 2019

Cure Spinal Cord injury latest therapies research, treatments 

PART I 

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

Update May 28th, 2019

Cure Spinal Cord injury latest therapies research, treatments 

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 the brain and spinal cord nerves.

 

1-Adipose cells – Mayo Clinic – Clinical trial Phase I (safety): RECRUITING PATIENTS (USA)

  • Background: The purpose of this study is to determine if mesenchymal stem cells (MSC) derived from the fat tissue can be safely administered into the cerebrospinal fluid (CSF) of patients with spinal cord injury. Adipose-derived mesenchymal stem cells (AD-MSCs) have been used in previous research studies at the Mayo Clinic but this is an experimental therapy for which it is necessary to check safety.
  • Latest update (May 2019): this trial is still recruiting, according to clinicaltrial.gov

Cure Spinal Cord injury latest therapies research, treatments 

2- Neuralstem Inc. – Neural Stem Cells – RECRUITING PATIENTS (USA)

  • 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 (May 2019): Dr. Ciacci was contacted for an update but we have not received any feedback so far. To date, the trial is still shown as recruiting patients on the clinicaltrial.gov website.  In June 2017, input from Neuralstem read With safety looking good, the green light has been given to treat more patients. “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 enrolment: 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 clinicaltrial.gov ((NCT01772810). Or scitrials.org/

    Cure Spinal Cord injury latest therapies research, treatments 

3- Nose Cells and Nerve Graft –Dr. Tobakow (Poland)- 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 of 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 (April 2019): 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, transplantation into the spinal cord and a peripheral nerve graft.
  • Patient enrolment (update April 2019): We received the confirmation by Dr. Tabakow that they have recruited one patient with a stab injury so far. His reconstruction surgery is under preparation. They are still looking for one more patient for the trial. Be aware: 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 trial 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 enrolment is available here: https://walk-again-project.org/#/en or on NCT03933072
  • UK TRIAL: 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.

Cure Spinal Cord injury latest therapies research, treatments 

4- Dr. Wise Young- Umbilical Cord Blood Stem Cells + combinations – Phase II clinical trial planned (USA) 

  • 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 command?).  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 (May 2019): Clinical trial in the USA in preparation: The FDA has granted approval for this clinical trial, and later this year, they will begin a trial with 27 subjects for this Phase IIb (aiming to prove efficacy) trial. It will consist of (info dated 2018, no update has yet been made available by the team responsible for the trial) three groups of nine, ASIA A, C5-T11 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. 
  • Patient Enrolment (update May 2019): This study is in preparation and is not recruiting patients yet. In order to qualify for this trial, you must have a complete injury between C5 and T11, be injured more than 1 year, 18-64 years old. There is no cost to participate in a clinical trial, but if selected, you would have to cover the cost of lodging and transportation in New Jersey (USA) for 6 months. Send e-mail to Jim Bennett who will add you to his list to be alerted when recruitment begins in a month or two. jimbenn@rutgers.edu” Source: Norcalsci.org

    Cure Spinal Cord injury latest therapies research, treatments 

5- NC1 – Bone Marrow Stem Cells Intrathecal Injection- Dr. Vaquero – New trial announced for incomplete SCI (Spain)

  • Background info:  Dr. 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). Various phase I/III trials have been carried out on both incomplete and complete spinal cord injury patients. More scientific details and detailed results can be found in the three following publications: 2016 publication (complete SCI) and 2017 publication (results for incomplete SCI), June 2018 publication (for both complete and incomplete SCI. According to the latter publication, the latest Phase II trial has shown varying types of (quality of life or clinical) improvement in all patients and resulted in significant improvement in three out of the nine patients measured (those changed from respectively Asia A, B, C Grades to Asia B, C, D (i.e. becoming more incomplete).
  • Latest Update (May 2019): According to the newspaper El Mundo (article in April 2019– translated from Spanish): “Today, after a long process involving a small group of people with this condition [SCI], they have announced the end of the development of a therapy [NC1] and its approval by the Spanish Agency of Medicines. Everything is ready to start working with 30 new patients [with an incomplete spinal cord injury]. “
  • Patient enrolment: This trial is not yet published on www.clinicaltrials.gov and is not yet recruiting. Beware: this trial will ONLY recruit patients from 18 years to 65 years with an INCOMPLETE SCI.

    Cure Spinal Cord injury latest therapies research, treatments 

6- Neuroplast (the Netherlands) – Autologous Bone Marrow from Stem Cells – Clinical research in preparation for both chronic and acute spinal cord injury – Human Trial announced in Spain and Denmark

  • BackgroundNeuroplast is an independent company founded in 2013 and is located on the Brightlands Maastricht Health Campus in The Netherlands. A preclinical study showed that Neurocells, the product of Neuroplast obtained from the patient’s own bone marrow, significantly improved both locomotor functions and survival in rats with spinal cord lesions compared to rats treated with placebo (drug without an active agent). Source: http://www.neuroplast.com/. The research involves the transplantation of Neurocells and will take place in two different centers: Toledo (Spain) and Copenhagen (Denmark). The Neurocells are expected to have a positive effect both in terms of neuroprotection and neuroplasticity and thus to contribute to a level of functional return in both chronic and acute spinal cord injury.

 

  • Last update (May 28th, 2019)Neuroplast is currently working on  phase II / III clinical trial in which 70 patients with (sub) acute spinal cord injury will participate. Phase II (16 patients) will start at the end of the summer of 2019. Phase III (54 patients) is expected to start 6 months later when Phase II is halfway.

 

  • Patient enrollment: Phase I has been completed and phase II / III of the study is in preparation. Patient recruitment has not yet started. The first 16 patients with chronic paraplegia are expected to be recruited by the end of the summer of 2019. These patients will be recruited around the centers (Toledo and Copenhagen) participating in the study.

 

Remarks/ Q&A: 

1. The first trials (chronic spinal cord injury) will take place in Copenhagen and in Toledo. Are patients from other countries also accepted? Complete or Incomplete spinal cord injury? The first trials are indeed going to take place in Copenhagen and Toledo and we are now working on a clinic in Halle (Germany) that can include patients from the end of the year. These are patients who are already being treated on the spot, so enrolling patients from other countries will be difficult. This concerns both complete (AIS A) and incomplete paraplegia (AIS B and C).

 

2.Will the other parts of the study (for acute and subacute paraplegia) also take place in Spain and Denmark? Or does a Dutch center participate? Or other countries? Both phase 2 and phase 3 will take place in the above-mentioned centers, we hope to work towards getting more centers (including the Netherlands) in our research, but for the time being nothing is concrete here.

 

3.”Phase I of the investigation has been completed”. Has phase I taken place somewhere? Our phase 1 has been completed without completing it because we have received the indication from the CCMO (Central Commission on Human Research in The Netherlands) that there are no consequences for the safety of the patient.

Cure Spinal Cord injury latest therapies research, treatments 

7- BioArctic – SC0806 (biodegradable device+ FGF1) – now in Phase II, recruiting patients- Sweden – Slovenia

  • Background info: SC0806 is a combination of a biodegradable medical device and a drug substance (FGF1) and nerve implant 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. BioArctic has received funding from the European Union’s Horizon 2020 Research and Innovation Program to carry out this project. The company also develops therapies for Alzheimer and Parkinson.
  • Update (May 2019): The company announced in February 2019 that “the first patient in the second panel of the Phase I/II study now has been treated with SC0806. This means that the study with the product candidate SC0806 for complete spinal cord injury has progressed into Phase II.
  • Patient recruitment (Complete traumatic SCI only): The inclusion of patients to the second of the three panels in the study is on-going. Each panel consists of six patients receiving SC0806 and three control patients. The treatment with SC0806 includes a surgical procedure. The surgery is followed by 18 months of intensive training in a robotic system to support nerve regeneration and muscle rebuilding in the part of the body affected by the paralysis. Patients receiving SC0806 are also given the option to participate in a 12 months extension study. An interim analysis of safety and efficacy of SC0806 in the first panel at 18 months is planned Q4 2019/Q1 2020.”  More info about this trial on clinicaltrials.gov: NCT 02490501., or on SCITRIALS.ORG Or contact: Hans Basun, MD, +46734411798, hans.basun@bioarctic.se

Cure Spinal Cord injury latest therapies research, treatments 

8- MD Stem-cells: Bone Marrow Stem-cells + virtual reality + rehab-Phase I clinical trial: RECRUITING PATIENTS  (USA)

  • Background: The SciExVR study will evaluate the potential benefit of autologous (patient’s own) bone marrow-derived stem cells (BMSC).The treatment consists of bilateral paraspinal injections of the BMSC at the level of the injury as well as superior and inferior to that spinal segment followed by intravenous injection and intranasal placement. Patients undergoing BMSC treatment may also be assigned to make use of exoskeletal movement (or equivalent) or virtual reality visualization (or equivalent) to augment upper motor neuron firing and/or receptivity of the sensory neurons. More info: http://mdstemcells.com/sciexvr/
  • Latest update (May 2019): 

9 – IPS* Cells– Safety clinical trial planned  (PHASE 1) (JAPAN)

  • Background: In February 2019, Japan’s health ministry approved the use of induced pluripotent stem cells (*IPS). The planned human trial comes after experimental transplants into monkeys by Keio University professor Hideyuki Okano and others succeeded in restoring motor function so that the animals could walk.
  • Latest update (May 2019):Plans call for the study to be conducted on four patients aged 18 and older who have suffered injuries to their spinal cord and whose sensation and bodily mobility have been completely lost. The researchers will develop cells that can grow into nerves from iPS cells stored at Kyoto University’s Center for iPS Cell Research and Application. Two million of these cells will be transplanted into the injured area of each of the subjects via injection. The research team will be led by Okano and Keio University professor Masaya Nakamura. The safety and efficacy of the procedure will be checked one year after the procedure, and the patients will undergo rehabilitation to help them regain motor control of their limbs. Immunosuppressant drugs will be used to control transplant rejection.”. Source: Nikkei Science
  • Patient enrolment: this trial is not published yet and is not recruiting patients yet.

    Cure Spinal Cord injury latest therapies research, treatments 

10-Schwann Cells and combinations – Miami Project- ACTIVE TRIAL BUT NOT RECRUITING PATIENTS

  • 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 (May 2019): 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.   Further studies are also in preparation and might involve the combination of Schwann cells with, respectively, growth factors, antibodies, and cell-support matrices.
  • Patient enrolment: This study is still active but not recruiting patients anymore, according to clinicaltrials.gov. For details,  see here: NCT02354625

Cure Spinal Cord injury latest therapies research, treatments 

11- Other STEM CELLS clinical trials in the world – Summary

  • China – Guangzhou  Umbilical Cord MSC transplantation – NCT03505034
  • Vietnam-  Danang  – Transplantation of autologous bone marrow-derived mononuclear cells by lumbar injection – Recruiting patients. More info: NCT02923817
  • China – Beijing  NeuroRegen scaffold with BMMCs or MSCs transplantation – more info: NCT02352077
  • China – Beijing – NeuroRegen Scaffold with bone marrow mononuclear cells (BMMCs). More info on: NCT02688062
  • China: Biological: Umbilical Cord Mesenchymal Stem Cells- Intrathecal administration of UC-MSCs- More info: NCT02481440
  • Brazil – autologous bone marrow mesenchymal stem cell transplantation – RECRUITING – more info:  NCT02574572
  • Jordan – Bone-marrow stem-cells – leukapheresis-derived, purified, autologous CD34+and CD133- more info: NCT02687672

Cure Spinal Cord injury latest therapies research, treatments 

12. Other active trials, but not recruiting patients: 

Cure Spinal Cord Injury latest therapies Research,  treatments, 2019

PART II

SCAR and GROWTH INHIBITORS REDUCTION & COMBINATIONS FOR REPAIR

Update: June 20th,  2019

Cure Spinal Cord Injury latest therapies Research,  treatments

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. Various peptides are also being tested for that purpose.

Additionally, this chapter also describes a few of the various therapeutic strategies that are used to neutralize growth inhibitors (often referred to as NoGo) after the spinal cord injury, and /or promote nerve growth.

Cure Spinal Cord Injury latest therapies Research,  treatments

1- ReNetX Bio – NOGO TRAP (CLINICAL TRIAL NOW RECRUITING PATIENTS)

  • 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 starting a clinical trial for cervical injury patients.
  • Latest update (June 20, 2019): ReNetX Bio has received the authorization to start their phase Ib – IIa clinical trial (meant to test safety and efficacy) for patients with a chronic Cervical Incomplete injury.  More info: ReNetX  announcement June 2019
  • Patient Enrolment: Various centers will recruit patients in the USA. More info on this trial can be found here: https://scitrials.org/trial/NCT03989440

Cure Spinal Cord Injury latest therapies Research,  treatments, 2019

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, or Ch’ase, has repeatedly been proven to degrade the scar, to promote growth and to improve recovery in animal experiments. 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 the Ch’ase therapy 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. 
  • Latest Update (April 2019): Two alternative gene delivery therapies (The gene for Ch’ase is expressed in an active form in human cells and can be switched on and off to ensure an optimal and controlled delivery) have been developed/ are being tested: 

a- The chondroitinase enzyme is delivered via a Lenti-virus vector (a harmless virus). The consortium demonstrated this therapy to give rise to improved walking and unprecedented upper limb function in rodent acute spinal cord injury models. See more information in this article and video and this Brain publication. The same treatment is currently being tested in a rodent chronic injury model (trial started in August 2018. Results will be shared in 2019). In parallel, work is carried out towards bringing this therapy to the clinics.

b- The Ch’ase enzyme is delivered via an Adeno-associated viral (AAV) vector which is already being used in other human treatments and would, therefore, obtain easier access to clinical trials. Various AAV vectors were created by Verhaagen’s lab and tested but they need further adjustment to retain the same functional efficacy as the LV vector.

  • Next translational steps:

-The AAV vector, once optimized, will be tested in both acute and chronic SCI models (rodents).

-Discussions are ongoing to test the best version of the chondroitinase therapy on humans. This is, however, a long-term goal. 

Cure Spinal Cord Injury latest therapies Research,  treatments

3-CRP (CSPG Reduction Peptide) possibly in combination with ISP– to reduce the scar –  Dr. Yu Shang Lee – Cleveland Clinic (Animal studies=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 (April 2019):  Further to initial testing of the CRP on a small number rats in 2017, Dr. Yu Shang Lee’s lab carried out additional studies on a larger number of rats (T8 chronic contusion SCI), as of August 2018. The project, co-funded by the endParalysis foundation, aimed to determine the efficacy of CRP alone and of CRP + ISP (ISP is another peptide, developed in Dr. Jerry Silver’s lab, Case Western University). Starting two-month post-SCI, the treated animals received the various peptides by daily subcutaneous injection during three consecutive months.
  • Results: Treatment outcome: The study shows an overall improvement in locomotor and bladder function in the treated animals. While there was a trend showing CRP+ISP works slightly better in improving BBB scores (testing stepping function) than CRP alone, there was, overall, no significant difference between the CRP+ISP and CRP groups. Importantly, both CRP and CRP+ISP groups demonstrated better hind limb/forelimb coordination).
  • Conclusion: The study seems to show that CRP enhanced connectivity established across injury site and nerve sprouting below the injured site after treatment, as well as an improved function for both locomotion and bladder (the CRP-treated groups show less hyperactivity, better void efficiency, and lower voiding pressures).
  • Next steps: Dr. Lee indicates the following steps will include

– testing dose responses of CRP to see if a higher dose can lead to an additional functional improvement,

– conducting Pharmacokinetics and Safety/toxicity tests of CRP

– testing the efficacy of CRP in a large animal model with Dr. Brian Kwon using pigs T10 subacute stage injury model (two weeks post SCI) to test both locomotion and bladder function

-testing the efficacy of CRP in a cervical chronic SCI model (C4 hemisection) to test forelimb/hand function in collaboration with Dr. Jerry Silver.

Cure Spinal Cord Injury latest therapies Research,  treatments, 2019

4-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 

Cure Spinal Cord Injury latest therapies Research,  treatments

5- DRUG ES 135 (PEPTIDE) – HUMAN TRIALS PHASE 3- CURRENTLY RECRUITING PATIENTS (TAIWAN) 

  • Background:  ES135 is a recombinant human acidic fibroblast growth factor (rhFGF1) with 135 amino acids. With its effect to promote neurite outgrowth, ES135 can be applied to the medical use of repairing neuron function. The sequence of ES135 has been patented by Eusol-biotech in Taiwan, EU, China, and the United States. 
  • Latest update (May 2019): A multi-centre, double-blind, randomized, placebo control study as the pivotal Phase 3 clinical trial for spinal cord injury patients is on-going and is expected to finish in 2024. Phase 3 is the last Phase before a possible approval for the drug to the market.
  • Patient enrolment: 100 patients with complete SCI are expected to be recruited. The patient recruitment criteria are not precise and do not indicate if the therapy is applied at the acute or chronic stage. More info: https://scitrials.org/trial/NCT03229031 

Cure Spinal Cord Injury latest therapies Research,  treatments

Cure Spinal Cord injury latest therapies Research, treatments

PART III

ELECTRICAL /MAGNETIC STIMULATION/TMS AND BMI/BCI

Update: 24 May 2019

Cure Spinal Cord injury latest therapies Research, treatments

Background informationE-stim (this term can refer to neuromodulation, neuro-stimulation, epidural stimulation), Magnetic stimulation, TMS (Transcranial Magnetic Stimulation) and BMI /BCI (Brain Machine or Computer Interface); all these technics use different protocols, involve various levels of invasiveness 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).

Cure Spinal Cord injury latest therapies Research, treatments

1-Epidural Stimulation with an implanted (Medtronic) stimulator- Many clinical trials ongoing/recruiting or planned:  

  • Background information: The patients receiving this kind of therapy undergo a surgery to transplant the electro-stimulation device (until now a Metronic electrostimulator, the same one as used for fighting neuropathic pain) over a certain part of the spinal cord (the section of the spinal cord stimulated with electric current differs depending on what the aim of the therapy is, for example, motor functions or bladder and bowel/ sexual function). Electro-stimulation of the cord is not a new system and was already used in some studies in 2000. However, the very first results of epidural stimulation with the Medtronic device were communicated in 2014. Since then many large scales clinical trials have begun and more are planned in various part of the world to check the isolated results published before. From the results known so far, E-stim should not be seen as a cure but rather as a way to enhance the quality of life. It does not repair the nerves but rather seems to stimulate the remaining connections. The interesting part of e-stim is that, in some limited cases, the (however limited) motor functions obtained through the stimulation when the e-stim device is on are actually seen to continue (for a limited time) after the device is switched off. 
  • Latest update (May 2019) / Results published/ documented so far: 
    • July 2015 (Dr. Harkema-Louisville- 4 patients- scope: motor control)– result for the first four patients were published (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 having 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.
    • May 2017 (Dr. Edgerton- a study on rats with Cervical injuries): the study highlights that e-stim may help people with a cervical injury to improve their grasp function, but it was conducted on rats only. Read more: here. 
    • November 2017 (Dr. Harkema – scope: Autonomic functions, including bowel-bladder and sexual functions): A poster was presented at the Neuroscience conference 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. 
    • October 2018 (Dr. Courtines – EPLF Switzerland and GTX Medical- results for 3 incomplete SCI patients): the study shows that targeted electrical epidural stimulation coupled with an intensive regimen of locomotor training can help people with incomplete spinal cord injury improve their mobility. More details in our article here.
    • October 2018 (Mayo Clinic – EES results for 1 patient): Nature Medicine reported that a single patient with a spinal cord injury at the Mayo Clinic was also able to take steps and walk with trainer assistance thanks to electrical stimulation and intensive physical therapy. Beware: in this study, the e-stim has to remain on for the subject to take a step. The electric impulse given by the surgically-implanted stimulator is necessary to take the step. More details in our article here
    • October 2018 (Dr. Harkema – University of Louisville. Results of Epidural Electric Stimulation + intensive training for 4 patients): According to the Louisville publication, all four patients treated achieved independent standing and trunk stability (with the stimulator on). One of them can actually walk a short distance on her own, with the stimulator on and with the use of a walker. Beware: the patient with the best outcome had a motor-complete, but sensory-incomplete spinal cord injury (she had sensation below the level of her lesion, which is not often the case and does indicate that a number of nerve fibers are actually intact). Beware: in this study, the e-stim has to remain on for the subject to take a step. The electric impulse given by the surgically-implanted stimulator is necessary to take the step. All details in our article here
    • March 2019 – publication by Dr. Darrow (Minnesota). First results of the E-stand trial – for two women with a complete SCI): What is outstanding in this study is that the therapy includes e-stim but does not include any particular physio-therapy regimen. The results in the field of locomotion seem to be in line with results reported so far (i.e., the ability to move limbs on command when the device sends impulses). In both cases, significant quality of life improvement is reported through a level of autonomic function improvement. More interestingly, one of the two women reported that she can now experience orgasm when the device is on. More info: here
    • December 2018 (Dr. Krassioukov, Canada- single patient (with motor-complete but sensory-incomplete injury. Scope: bladder and bowel function). The 2018 publication mentions a positive effect of neuromodulation applied on the lumbosacral cord to modulate autonomic circuits involved in the lower urinary tract and bowel control after SCI. The study reports improvement of both urinary tract and bowel routine for this single patient, for example in terms of urodynamics (which could also result in a lower risk of a bladder infection) and a much shorter time needed for bowel routine. Although this improvement can be of value in terms of quality of life and care, rather than in terms of actual recovery, the study does not show an actual full recovery of the bowel and bladder function.

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  • Patient enrolment (update May 2019): 
    • Minnesota – 100 patients: According to the E-stand website, the trial is still 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
    • 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. 
    • Kentucky (The Big Idea/ Dr. Harkema): It is not clear whether this project (36 patients anticipated) for which Reeve foundation has been raising funds since 2014 is actually (still) recruiting patients nor how many patients are already enrolled or what results have been obtained so far. 
    • Switzerland (Stimo- Dr. Bloch, Zwitserland/ GTX Medical) is still recruiting participants with an incomplete spinal cord injury (ASIA C or D–level T10 or higher).  Most patients have already been recruited and have received the therapy (see the first results above) but this trial is still shown as recruiting. 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
    • Europe – future steps (Medium term) planned by GTX Medical (Switzerland and The Netherlands – Dr. Courtine). 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. According to GTX’ CEO Sjaak 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.
    • Europe – STIMO 2 study: GTX Medical and the Sint Maarten Kliniek in Nijmegen (the Netherlands) recently announced that a study was expected to start and will recruit people who have just acquired an incomplete spinal cord injury at T10 or higher. Be aware: ACUTE (very recent) and INCOMPLETE injuries only. This study is expected to start around September 2019, in Nijmegen.

2-Transcutaneous e-stim (non-invasive): 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.   

(*) Risks:  it has to be stressed that one patient, however, has reported a dramatic increase in 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 (update May 2019): It is a (not so) well-kept secret in the field that the NRT company who was raising funds to be able to develop and carry out a transcutaneous stimulation clinical trial in the USA might be merging with another company in the field of EES. Meanwhile Dr. R. Edgerton just founded another start-up company with just the same goal: SpineX. Professor Edgerton now also spearheads a program in Australia along with Professor Bryce Vissel. It is not clear yet if that program will be focusing on solely transcutaneous e-stim or a combination of various kind of e-stim.
  • Latest results (update May 2019): 
    • July 2015: Dr. Reggie Edgerton’s group and 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.
    • May 2019 -From the Recovery Research Program website: “In a world-first, Professor Edgerton and his team have re-awakened the spinal cord and successfully restored feeling and function to more than 20 paralyzed people using non-invasive neurostimulation. Six of his patients have recovered hand movement, bladder and bowel control, sexual function and the ability to stand – unprecedented results in the history of medical science.”. As far as we know though, there is no scientific publication yet published regarding these results. The recovery of some level of hand movement and ability to stand, with the stimulator on, is a rather clear and expectable result from sending an electric impulse through the stimulator. However, the website does not say what status the patients were in before the therapy (i.e., acute or chronic SCI – Complete or Incomplete SCI). Also, we can and should remain cautious as to “recovered bladder and bowel control, sexual function”, a concept which is so far not accurately defined or proven and might differ greatly from patients’ expectations.
  • Patient enrolment (update May 2019): A few clinical studies using transcutaneous stimulation are underway or planned in various countries:
    • Switzerland – Second panel of the Stimo study – Dr. Bloch- University of Zurich Beware: patients with INCOMPLETE SCI only – Click for details: NCT03137108
    • The USA – UCLA: This study focuses on the potential improvement of bladder control following transcutaneous stimulation: NCT02331979
    • USA – Shepherd Center NIH: Only recruits patients with an Incomplete SCI level T12 and above.  Click for details: NCT02340910 
    • Australia- Recovery Research Program (previously  Project Edge:  UTS and Professor Bryce Vissel). The Program is being spearheaded by Professor Reggie Edgerton and Professor Bryce Vissel, who lead an international team of world-class scientists and health professionals at UTS’s Centre for Neuroscience and Regenerative Medicine. It is the first comprehensive and clinical enterprise outside the United States of Professor Edgerton’s ground-breaking research into neurostimulation to re-awaken the spine and successfully restore feeling, function, and movement in spinal cord injury patients. This program is expected to start and to recruit patients soon.

Cure Spinal Cord injury latest therapies Research, treatments

3- Transcutaneous Magnetic stimulation of the lower spine (non-invasive) for improved bladder function- Dr. Lu – UCLA (USA)

  • Background information:  In August 2018, neuroscientists were reported to have restored “significant bladder control” by five men with spinal cord injury. “We were excited to see a positive effect in all five patients after only four sessions of mild magnetic stimulation,” said Dr. Daniel Lu, the study’s principal investigator and an associate professor of neurosurgery at the David Geffen School of Medicine at UCLA. “The benefit persisted from two to four weeks, suggesting that the spinal cord’s neural circuitry retains a ‘memory’ of the treatment.”  While magnetic stimulation is quite similar to e-stim,  Lu’s team used magnetic stimulation because it’s noninvasive, painless and less costly than an electrical implant. Source: see this article

 

  • Latest update/Results so far (Update May 24, 2019): “All five of the men regained the ability to urinate on their own during stimulation,” Lu said. “One patient — 13 years after his injury — was able to completely stop using a catheter and empty his bladder several times a day, up to four weeks after his last treatment.” For more detail see the August 2018 scientific publication here. The conclusion of that publication is that “neuromodulation of spinal micturition circuitry by TMSCS may be used to ameliorate bladder function”.The ability to urinate at will improved in each patient. Four of the men still had to use a catheter at least once each day — but that was still a significant drop from their average of more than six times a day before the treatment.

 

  • Patient enrolment (Update May 2019): To our knowledge, many more patients have undergone the therapy and have shown progress. We are not aware of the current recruitment schedule but the clinicaltrials.gov website shows a still active trial in that field. See scitrials.org NCT02331979

Cure Spinal Cord injury latest therapies Research, treatments

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

  • Background informationTMS 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 (May 2019): There are several studies underway (see below) in Cleveland, Boston and elsewhere in the world to evaluate TMS therapy spinal cord injury and other nervous system disorders.
  • Patient enrolment: 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 – This trial is shown as completed – results have not yet been published
    • 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): active but not recruiting patients. For 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 – Trial status is unknown

Cure Spinal Cord injury latest therapies Research, treatments

5-Brain-Machine Interface (BMI) – Walk Again Project (WAP) – Dr. Miguel Nicolelis in Brazil

  • Background infoWe 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. […] – 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. More info on this website.
  • Latest Update (14 May 2019): See the latest update about this project here.  According to this article: “Two patients with paraplegia regained the ability to walk with minimal assistance, through the employment of a fully non-invasive brain-machine interface that does not require the use of any invasive spinal cord surgical procedure”.
  • Patients enrolment (May 2019)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.

Cure Spinal Cord injury latest therapies Research, treatments

6- Melbourne, Australia “SWITCH” Clinical study – BMI – STENTRODE/ BIONIC SPINAL CORD – RECRUITING PATIENTS

  • Background informationUniversity 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 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 in this video.
  • Latest update (May 2019):  According to the website: “An early feasibility study of the safety  (phase I trial) of the Stentrode™ device in participants with loss of motor function due to paralysis from spinal cord injury, motor neuron disease, stroke, muscular dystrophy or loss of limbs. The purpose of this research is to evaluate the safety of the Stentrode™ device in humans. This is an experimental device. A new medical device and surgical technique have been developed, which allows implantation of the electrical sensors without open brain surgery. The device, called Stentrode™, is a small metallic mesh tube (stent), with electrode contacts (small metal disks) within the stent structure. It can be placed inside a blood vessel of the brain located in an area that controls movement (motor cortex). This does not involve open brain surgery. This research will be the first of its kind to be performed in humans and may help us find safer, more effective ways to introduce/implant electrical sensors in patients’ brains”.
  • Patient enrolment: SWITCH clinical study (10 patients, including a few SCI patients) More info on patient enrolment here or email to christin.bird@mh.org.au

Cure Spinal Cord injury latest therapies Research, treatments

7-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 (May 2019): The first quadriplegic patient recruited within the trial was operated upon on June 21st, 2017.  An announcement by A.L Benabid, MD, Ph.D., during the latest WSSFN Congress in Berlin. More info on the Clinatec website: here
  • Patient enrolmentThis trial is still recruiting patients, according to clinicaltrials.gov.  Be aware, candidates should be quadriplegic, aged 18-40 and fluent in French, among other criteria.  More info: NCT02550522

Cure Spinal Cord injury latest therapies Research, treatments

PART IV-

COMMERCIAL/ UNPROVEN THERAPIES

Cure Spinal Cord Injury Research, therapies, treatments, 2018

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.

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

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