Background info: 

A first study was carried out on patients in 2019 to check the safety of mesenchymal stem cells (MSC) derived from fat tissue (autologous cells, i.e. from the patient him/herself) and to see if they could be safely administered into the cerebrospinal fluid (CSF) of patients with spinal cord injury. The trial had unexpected results on one patient with a chronic incomplete spinal cord injury. He had already recovered some functions but was still wheelchair-bound and had plateaued in his recovery. He gained major functions back after the Adipose-derived mesenchymal stem cells (AD-MSCs) transplant. More results about this particular case to be read here. It is to be highlighted that this is only one patient and that the other patients involved in the trial have not shown similar improvements.

Latest update (May 2022):

A new trial was launched in 2020 to check both safety and efficacy of the Adipose-derived mesenchymal stem cells (AD-MSCs) intrathecal delivery (i.e. through a puncture) on more patients with spinal cord injury, complete or incomplete. This trial is randomized, meaning that not all participants will get the same /full treatment. However the crossover design ensures that the people who first receive only physical training (control group – no stem-cells), will later on be given a single injection of stem cells (six months after their injury).

Patients enrolment (update May 2022):

This trial is still recruiting and is expected to deliver full results in 2024. From the selection criteria, it seems that this trial recruits patients who have had a certain level of recovery after their trauma, but who have now plateaued. For further info, go to  NCT04520373

Background info:

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 (Sept 2021):

As far as we know, one patient had been recruited and operated upon in 2019, but the outcome of the treatment has not been communicated nor published. The clinical trial would follow the same protocol as the one applied to the original patient, i.e. extraction of olfactory cells from the olfactory bulb in the patient’s brain, transplantation into the spinal cord along with a peripheral nerve graft.  One more chronic SCI patient is still being recruited for this clinical trial taking place in Poland (Dr. Tobakow).   The Walk-Again website concerning this trial has not been updated for a few years but the Nicholls Spinal Injury Foundation communicated  some delays in their 2020 newsletter:” […] challenges faced by the Walk Again Project in Poland in 2019. The nature of the work means the project must adhere to EU legislation issued by the European Medicines Agency (EMA). In order to meet the strict criteria, new high-tech equipment and upgrades to the laboratory were required. All equipment has now been purchased; it is just the complicated work on the ventilation system that remains. This work is being carried out by the Wroclaw Medical University and as such is outside of our direct control”.

Patient enrolment (clinical trials)- update Sept. 2021:  

– In Poland: Only for patients with a transected /severed spinal cord.  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

– In the UK: complementary research on OEC’s – 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. One publication was made regarding the combination of OEC’s transplant with a biomaterial, and concludes the following (based on an animal study):
“Combination of OECs with biomaterials such as collagen increases the transplant size significantly without affecting the neural repair capacity of OECs. This improves the prospect of transplantation of OECs to bridge a larger surface area of injured spinal cord such as those seeing in human contusion injuries. Elongation of OECs guided nanofibers providing directional pathways may be more efficient in promoting regeneration of nerve fibers in spinal cord injury.” Read more here.

Background info:

In February 2019, Japan’s health ministry approved the use of induced pluripotent stem cells (*IPS). IPS cells are created by reprogramming cells from body tissue to revert to an embryonic-like state, from which they can develop into other cell types such as nerve cells. They are shown to have regeneration potential comparable to embryonic stem-cells but do not involve an embryo, hence being far less controversial. 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 (January 2022):

The clinical trial was expected to start in 2021 but had to be delayed because priority was given to COVID patients. This trial is interesting because it will be the first time that IPS cells are used to treat spinal cord injury (they have already been used to treat other conditions). In a Sept. 2021 scientific publication, we learn that the trial will focus on sub-acute SCI patients, which is within two to four weeks of sustaining a spinal cord injury. Hopefully, chronic SCI patients can also be included at a later stage but there is no mention of that. This study is a phase I clinical trial, thus is mainly aimed at checking whether the therapy is safe. The article states: “The primary focus of this clinical study is safety, and the number of transplanted cells may be too low to confirm efficacy. After confirming safety, a dose-escalation study is planned.” 

In January  14th, 2022, the very first patient is reported to have had the surgery and to be doing well. According to France24, « The patient will be monitored by an independent committee for up to three months to decide whether the study can safely continue and others can receive transplants ».

Patient enrolment/Clinical trials:

This trial is not published yet in clinicaltrials.gov. The abovementioned publication states “We plan to start recruiting a patient as soon as the COVID-19 epidemic subsides”. In total, four patients are expected to be recruited.

Background info:

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 2022): 

Clinical trial in the USA in preparation. According to communication in May 2021, the team had obtained the authorization from the FDA to carry out the trial. However because of COVID-19, the trial sponsor backed out and they are now working on the new IND and raising money for the trial. In a recent presentation (Sept. 2021), Dr. Young has indicated that the trial will now involve more patients (40 people) and  include a control group (a number of patients who will NOT receive the stem-cell treatment). Another change compared to previous plan is that no lithium treatment will be included for any patient to simplify the protocol. The latter will only include the UCB stem-cells and/or the intensive physiotherapy.

The trial was expected to start in January 2022. However, it has recently been announced that StemCyte, the company providing the stem-cells, pulled out of the USA trial. As a consequence, the team has to find a new source of umbilical cord blood stem cells and has  to go through the IND approval process from the beginning. The FDA is requiring an additional study to prove the new sources of cells are also safe and effective. Hope to start the trial later this year., thus still needs approval from the FDA (and funding from sponsors).

Patients enrolment (update May. 2022):

This study is in preparation and is not recruiting patients yet. These are the recruitment criteria as previously communicated (beware that they might have been adjusted): 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. For more info, email:  sciproject@dls.rutgers.edu”

PS: the biotech company who pulled out of the clinical trial plan has actually launched their own clinical trial, but in Taiwan and is currently recruiting patients in Taiwan. More info here: NCT03979742

Background info:

Vaquero (M.D. Puerta de Hierro University Hospital, Spain) has been studying the impact of the autologous (from oneself)) 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 (Sept. 2021): 

In 2019 the newspaper El Mundo indicated that  (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]. They also reported that “The number of patients will gradually rise over the following years, in a process which is dependent on submitting regular reports and an assessment of the outcomes.”  

Unfortunately, Dr. Vaquero passed away in 2020 and it is not clear what the consequences are on the clinical trials. Some information about the trials is available though, on the following page in Spanish.

Patients enrolment (Clinical trials): 

This trial is not yet published on clinicaltrials.gov and is not yet recruiting. Beware: this trial would ONLY recruit patients from 18 years to 65 years with an INCOMPLETE low SCI (T or L level). It is possible that the trial recruits only candidates from Spain. If you are interested, we advise you to check all information on this page in Spanish   (which also includes an application form for the NC1 therapy clinical trial)

Background info:

Neuroplast 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.

Latest update (May 2021):

In March 2022, Neuroplast announced that they just enrolled their first patient in a Phase II clinical trial to evaluate the efficacy of their stem-cells treatment on acute Traumatic Spinal Cord Injury. In November 2020, Neuroplast had already reported that their first patient with chronic spinal cord injury had been treated with Neuro-Cells in Toledo, Spain, as phase I of the trial, showing the safety of the therapy.  The current phase II/III is expected to enrol further patients in Spain and Denmark.

Patient enrolment/clinical trials:

The new trial, involving people with a traumatic acute / sub-acute spinal cord injury (6-8 weeks after lesion) is now recruiting in Spain. It is not yet recruiting in Denmark. More info on NCT03935724.

Chronic SCI:  at this moment we do not know if another specific clinical trial will be organized for patients with a chronic spinal cord injury. However, it is interesting to highlight that the trial that just started will recruit patients in their sub-acute phase (6-8 weeks after SCI) but will also test whether the therapy works during the chronic phase. Indeed, the protocol is designed in such a way that the patients who are in the control group get a placebo (no stem-cell treatment) at sub-acute stage, but they do get the stem-cell treatment six months after injury. So although, chronic SCI patients will not be able to enrol this trial, it will nevertheless test the therapy at chronic stage thanks to this « early and late intervention cross-over design », which is very interesting.

Background info (Nov 2021):

A scientific paper was published in 2021 featuring « Dancing Molecules » and their ability to « reverse paralysis ». The focus of the experiment was on rodents with a severe acute SCI. A video shows rats walking again 4-6 weeks after the injection (though their movement is by far not back to normal, so the term « reverse paralysis » seems to be overrated. The discovery, by Dr Samuel Stupp (North Western University) attracted major media attention. This « injectable therapy » is based upon « super-molecular chemistry » and nano-medicine (the injected material looks like water, but it contains nano-filaments/ nano-fibers and turns into a gel as soon as it touches the body cells). Super-molecules are an ensemble of thousands of molecules brought together. The injected molecules are also specially designed with signals. In the spinal cord, cells have receptors on their membranes and are constantly moving. So, the therapy is also designed to allow the injected molecules to move and follow the spinal cords cells. The researchers claim that the therapy have the following five effects (for rodents, in an acute SCI setting):

– regenerating axons after an severe acute spinal cord injury
– enhance vascular growth (blood vessels inside the cord)
– remyelinate the axons
– save a lot of motorneurons (necessary to enable movement)
– diminish glial scar.

Latest update (May 2022):

In various interviews early 2022, Dr Samuel Stupp indicated that his goal is to test the therapies on humans. His lab has received a funding to prepare for the IND (application to the FDA to review and possibly authorised the therapy to be tested on humans). Since this treatment involves a really big number of molecules put together rather than a single molecule, it will be interesting to see how the FDA responds to this proposal. Another interrogation remains as to how the injection would be made into the human spinal cord. Would it be an injection through the dura (the envelop protecting the spinal cord)? Dr Stupp indicates that the matter would have to be discussed with neuro-surgeons.

Besides, Stupp informs that he is willing to test the therapy on chronic SCI as well, which is a good news. However, no timeline is known so far.

Patient enrolment/ Experimental trial- NOT YET:

The lab’s target is to go to clinical trial with the therapy. However, given the innovation level of the treatment, it can be expected that it will take quite some time to actually start human trials.

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 in 2018/2019.  There is no other such case reported to-date and this can probably be considered as an exception, albeit a painful one.

As announced in our previous overview, the NRT company who was raising funds to develop and carry out a transcutaneous stimulation clinical trial in the USA has merged with another company, now known as ONWARD.  Meanwhile Dr. R. Edgerton 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.

Results known so far (update MAY 2022 – non-exhaustive):

• February 2020: Dr. Edgerton and Dr. Parag Gad show that “We found that TESCoN [the non-invasive transcutaneous e-stimulation therapy offered by the SpineX company, led to decreased detrusor overactivity, improved continence, and enhanced LUT [Lower Urinary Tract] sensation across the different pathologies underlying LUT dysfunction. This study serves as a pilot in preparation for a rigorous randomized placebo-controlled trial designed to demonstrate the effect of TESCoN on LUT function in neurogenic and non-neurogenic conditions”. To be noted that the trial was carried out on 14 patients with LUT dysfunction, 5 of whom with spinal cord injury (other patients had other pathologies, e.g. MS). We not talking about recovery of bladder function here but rather of an improvement of the symptoms. Read more in this 2020 publication.

• May 2019 -On the Recovery Research Program website (page is now disabled), it read: “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.” Once again it appears that the announcement was rather unprecise and very misleading. The only publication we found, is focusing on six patients only. It is noteworthy to add that these patients all had an INCOMPLETE spinal cord injury (Asia B or Asia C).  The publication (Sept. 2018) does document solid hand-grip improvement in all six patients and mentions some improvement in autonomous functions. 

• 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.

Patient enrolment (update May 2022): 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 – active but not recruiting

• USA – Shepherd Center NIH: Only recruits patients with an Incomplete SCI level T12 and above and aims at checking dose-response (check the impact of amount/intensity/frequency of transcutaneous e-stim on the potential improvement for the patients.  Click for details: NCT04697472
• USA, CANADA, EUROPE (including the Netherlands and UK) – UP-LIFT trial: The Up-LIFT Study is a study designed to evaluate the safety and effectiveness of non-invasive electrical spinal cord stimulation (ARC^EX Therapy, offered by the ONWARD company) administered non invasively (through the skin) to treat upper extremity functional deficits in people with chronic INCOMPLETE tetraplegia. Recruiting patients with non-progressive spinal cord injury from C2-C8 inclusive. They plan to enrol 65 subjects in total. The study is currently recruiting. More information on NCT04697472

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 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 non-invasive, 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 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 2022):
To our knowledge, many more patients have undergone the therapy and have shown progress. This trial is still recruiting patients (USA). We are not aware of the current recruitment schedule but the clinicaltrials.gov website shows a still active trial in that field. See  NCT02331979 – recruiting

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 (May 2022): 
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 human trials are recruiting patients, for example:

• University of Miami NINDS:NCT02446210 – Recruiting
• University of Zurich (recruiting patients with an incomplete SCI, T10 and above. The study tests the effect of deep-brain stimulation on locomotion): NCT03053791 – recruiting
• 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