Regenerative stem cell technology aimed at treating traumatic spinal cord injury is moving closer to reality with enrolment beginning in its Phase II clinical trial.
The pioneering Neuro-Cells® therapy aims to reduce irreversible damage to the central nervous system from secondary inflammation following trauma.
Having produced “positive” Phase I results, the first patient has now been enrolled in Phase II, to evaluate efficacy of the treatment created by Dutch biotech Neuroplast.
Neuroplast also revealed that, in addition to the potential of Neuro-Cells in spinal cord injury, it hopes to attract the funding to expansion into traumatic brain injury (TBI) and Frontotemporal Dementia.
Neuroplast CEO, Johannes de Munter, said: “The start of this Phase II trial marks another important milestone in our mission to bring back perspective to people who suffer from neurodegenerative diseases, for which no effective treatments are available.”
The Phase II trial will involve 16 patients who will be included six to eight weeks after sustaining trauma to the spinal cord.
Spanish and Danish authorities have approved a combined Phase II/III clinical trial, which enables a faster development path towards the market.
Dr Antonio Oliviero, principal investigator at Hospital Nacional de Parapléjicos de Toledo, Spain, said: “After having worked in the field of Spinal Cord Injury for almost 20 years, I am happy to contribute to establishing the role of cell transplantation in the functional recovery of individuals with spinal cord injury.
“I am excited to be a part of this new step in research, together with Neuroplast.”
Annually, approximately 29,000 people across Europe and the USA sustain acute TSCI, which can lead to paralysis or other disability.
To help give hope to patients affected by spinal cord injury, Neuroplast – founded in 2014 by physician Johannes de Munter and neurologist Erik Wolters – developed Neuro-Cells, a treatment that uses the patient’s own stem cells to prevent further loss of function during the acute phase after sustaining damage to the spinal cord, to preserve function, mobility and independence.
Now in Phase II trial, the study is a randomised and placebo-controlled trial, with intervention group receiving Neuro-Cells in the sub-acute phase after sustaining trauma, with six months follow-up to their primary endpoints.
The placebo group will receive a placebo at first, but will be treated with Neuro-Cells after the initial six-month follow-up period.
Electrical stimulation improves arm control in paralysed monkeys
Groundbreaking research highlights the impact on upper limb motor control
Electrical stimulation of surviving nerves of the upper spinal cord damaged by severe injury can improve motor control of the upper limb and allow those with limited arm function to partially regain lost movement, groundbreaking new research has revealed.
In a study with macaque monkeys, analysis showed that, while not enough to restore the arm function completely, stimulation significantly improved precision, force and range of movement, allowing each animal to move its arm more efficiently.
Importantly, the animals continued to improve as they adapted and learned how to use stimulation.
“To perform even the simplest arm movement, our nervous system has to coordinate hundreds of muscles, and replacing this intricate neural control with direct electrical muscle activation would be very difficult outside a laboratory,” said senior author Dr Marco Capogrosso, assistant professor of neurological surgery and member of the Rehabilitation and Neural Engineering Labs at the University of Pittsburgh.
“Instead of stimulating muscles, we simplified the technology by designing a system that uses surviving neurons to restore the connection between the brain and the arm via specific stimulation pulses to the spinal cord, potentially enabling a person with paralysis to perform tasks of daily living.”
Deficits in arm and hand mobility—ranging from limitations in bending the wrist to completely inability to move the arm—can severely impact a person’s life with even mild deficits to arm and hand function significantly limiting patients’ quality of life and their autonomy, making restoration of upper limb control an important focus in the field of neuro-rehabilitation.
Pitt researchers sought to develop a technology that could activate the remaining healthy nerves connecting the brain and the spinal cord to control muscles of the arm using external stimuli.
The technology – which follows ONWARD in its groundbreaking use of spinal cord stimulation – also had to be seamless and require little to no training to use, allowing the individuals to continue familiar motor tasks the way they did before their injury.
To test the technology, researchers worked with macaque monkeys with partial arm paralysis who were trained to reach, grasp and pull a lever to receive their favorite food treat.
In addition to brain implants detecting electrical activity from regions controlling voluntary movement, the monkeys were implanted with a small array of electrodes connected to an external stimulator the size of a pencil-top eraser, which were transiently turned on when brain electrodes detected the animal’s intention to move its arm.
“Our protocol consists of simple stimulation patterns that are initiated by detection of the animal’s intention to move,” said co-first author Dr Sara Conti, at Harvard Medical School and Boston Children’s Hospital.
“We don’t need to know where the animal wants to move; we only need to know that they want to move, and extracting that information is relatively simple.
“Our technology could be implemented in clinics in many different ways, potentially without requiring brain implants.”
The electrodes and the stimulator’s design and placement—over the nerve roots sprouting from the spinal cord toward the muscles of the arm and hand—were extensively verified using a combination of computational algorithms and medical imaging, ensuring that each animal’s unique anatomy was compatible with the device.
“Taking a step back and tackling a very complex clinical problem from a different and simpler perspective compared to anything that was done before opens more clinical possibilities for people with arm and hand paralysis,” said co-first author Dr Beatrice Barra, visiting scholar at Pitt, currently at New York University.
“By building a technology around the nervous system that mimics what it is naturally designed to do, we get better results.”
A clinical trial testing whether electrical spinal cord stimulation could improve arm and hand control in patients who have had strokes is recruiting participants at the University of Pittsburgh and UPMC.
ONWARD launches latest pioneering trial
LIFT Home Study explores potential for its ARC EX spinal cord therapy in a home-based setting
The development of pioneering stimulation therapy for people living with spinal cord injury (SCI) is continuing with ONWARD completing enrolment for its latest groundbreaking trial.
The LIFT Home Study is designed to study the safety and performance of ONWARD’s ARC EX therapy when used in the home.
ARC EX works by externally delivering programmed stimulation of the spinal cord to restore strength and function in people with SCI and other movement related challenges.
It has already been in trial in a medical setting through the Up-LIFT pivotal trial enrolling 65 people internationally ahead of schedule, despite the challenges presented by the COVID-19 pandemic, and is already yielding strong initial results.
Its ARC IM implantable technology is also in trial, with its STIMO-BRIDGE study enabling three long-paralysed patients to regain the ability to take steps independently after one day, and to swim and/or cycle after five months of rehabilitation.
The LIFT Home Study has enrolled 17 participants at five leading research centres in the United States – Craig Hospital in Denver, Colorado; Shepherd Center in Atlanta, Georgia; Spaulding Research Institute in Boston, Massachusetts; University of Minnesota, and University of Washington.
Participants were followed for four weeks to assess whether continued access to ONWARD’s ARC EX therapy is safe and can be used to achieve long-term benefit.
The trial builds further on the commitment of ONWARD, based in Lausanne in Switzerland, to regain function and independence for those living with SCI. Plans remain on track for its ARC EX technology to be commercialised next year.
Dr Candy Tefertiller, executive director of research and evaluation at Denver’s Craig Hospital is primary investigator, and said: “The LIFT Home Study is an important next step in understanding the potential benefits people with spinal cord injury may derive from continued access to ARC Therapy outside the clinic.
“We are pleased enrolment is now complete and we look forward to completing follow-up activities.”
“We are grateful to collaborate with these outstanding researchers to investigate new potential benefits and care settings for our ARC EX therapy,” said Dave Marver, CEO of ONWARD.
“This is another step in our journey to help people with spinal cord injury regain function and independence.”
ONWARD – making the impossible possible
CEO Dave Marver discusses its pioneering work in spinal cord injury and the new hope for people living with paralysis
The concept of three people living with complete paralysis regaining the ability to walk independently is something that, in the very recent past, would have been dismissed as being impossible – but through the work of ONWARD, this one-time ‘impossibility’ is now becoming reality.
For years, spinal cord injury has been regarded by many as the ‘graveyard of neuroscience’, where hope was in short supply and the outlook for those daring to dream of the day that may change was bleak.
But now, through the efforts of pioneers who have led the research breakthroughs that are now shaping reality, the ability of technology to change lives is being seen by the whole world, with people watching in amazement as paralysed patients rediscover the ability to move.
After being implanted with spinal stimulation technology developed by ONWARD – the first time its epidural electrical stimulation (EES) had been trialled in humans – all three participants who were part of the STIMO-BRIDGE trial were able to take steps independently within a single day.
After five months of rehabilitation, they were also able to use their legs to stand, walk, swim, and/or cycle. They also regained control of their trunk muscles.
Such colossal steps forward in SCI are now giving new hope to people living with paralysis – and are helping to show, rather than being impossible, what could become the new possible for the future.
“We were very pleased with the results of STIMO-BRIDGE, although we as a company are not going to be pleased with just impacting subjects in a clinical trial,” Dave Marver, CEO of ONWARD, tells NR Times.
“Our job and our unique role is to scale these therapies so they can provide benefit to hundreds of thousands of people with spinal cord injury around the world.
“These results show great promise, but we still have a tremendous amount of work to do to achieve our vision.”
And for ONWARD, that vision is to change the lives of people living with SCI globally, to enable them to enjoy and live their lives in the ways that matter most to them.
Established in 2014 to focus specifically on SCI, the venture has led truly groundbreaking research into this long-underserved area.
Founded by neurosurgeon Dr Jocelyne Bloch and Professor Gregoire Courtine, Swiss-based ONWARD has taken decades of research and translational science to bring to fruition two viable commercial solutions.
With its ARC EX and ARC IM devices, ONWARD – backed by many of the leading European life sciences venture capital investors – has led the charge on redefining the outlook for SCI patients.
Its ARC IM, recently subject to the STIMO-BRIDGE trial, consists of an implantable pulse generator and lead that is placed near the spinal cord, controlled by wearable components and a smartwatch. A pivotal trial is set to begin within the next 12 to 18 months.
The ARC EX is an external, non-invasive wearable stimulator and wireless programmer, which targets the rediscovery of upper body movement. Currently subject to the international Up-LIFT trial – the largest SCI trial of its kind – it completed enrolment of 65 participants ahead of schedule, despite the many challenges presented by the COVID-19 pandemic.
Currently being trialled at sites across the world – including in the NHS Greater Glasgow and Clyde (NHSGGC), as well as Neurokinex sites in England – the aim, pending necessary approvals, is for a commercial launch in the first half of 2023.
But while the excitement at the potential of ONWARD is palpable, with the first introduction of its technology into rehabilitation centres across the United States, UK, France, Germany and the Netherlands potentially barely a year away, Dave is keen to ensure expectations remain realistic.
“Certainly this will give hope to people, and I think the fact we enrolled all 65 subjects in Up-LIFT ahead of schedule, despite all the challenges of clinics closing and difficulties with quarantines and so forth, speaks to the enthusiasm that the clinical community has for this therapy,” he says.
“They have really embraced it, as the participants did in STIMO-BRIDGE. We, and they, are showing what is possible.
“But I do think it’s important to not overstate it, I don’t want to create false hope, because these subjects really committed themselves to the therapy and to the rehabilitation process.
“I think there is great potential that many people with paralysis will be able to stand again with the benefit of our therapies, maybe take some steps. But then it really depends on their particular circumstances and their overall level of health, their willingness to commit to rehabilitation, whether they can go further than that.
“And, of course, not everyone with spinal cord injury, desires necessarily to walk again, they may have other priorities. And that’s why ONWARD is also committed to addressing other challenges that affect the quality of daily life, such as blood pressure and trunk control and use of better use of the upper extremities.
“And then in the future, we’ll be looking at incontinence and restoration of sexual function, the whole battery of things that people with SCI have to contend with.”
Through its longstanding and deep-rooted commitment to the SCI community, ONWARD has secured relationships with of some of the world’s leading organisations in this area, including the International Spinal Research Trust and the Christopher & Dana Reeve Foundation. The latter has even become ONWARD shareholders, to help further its pioneering work.
For Dave, while the word ‘pioneering’ is well-used, for ONWARD, it is also well-earned.
“I think we are seen as pioneers in this area because we’ve chosen to focus on serving the spinal cord injury community,” he says.
“It’s a smaller population than other populations with movement-related challenges, like stroke and Parkinson’s, for example. Most businesses orientate toward the largest potential markets, whereas our founders really had a passion for helping people with spinal cord injury.
“And that remains the core vision, that was their raison d’être, and it’s with that commitment and determination that we have achieved such progress.
“We haven’t partnered with existing spinal cord stimulation companies, we’ve developed our own technology platform that is built for the specific purpose of not stimulating the spinal cord for pain management, but stimulating the spinal cord to restore strength and function.
“But I think the progress we have made also reflects the close collaboration that we enjoy and value with our scientific partners. We have a group of people so committed and driven by our mission, which I think is why we make the progress we have done.
“We develop that lead together in a very rigorous way, with our vision at the heart of that.”
Constantly looking to the next innovation and how its technologies can be even more beneficial to those who need them, ONWARD is also considering how, post-commercial launch, its ARC EX could be used remotely.
“Later, we’ll be seeking approval for it to be used in people’s homes, so they can conduct periodic sessions maybe once or twice a week in their homes to continue gains that they have observed in the clinic, and build on those gains,” says Dave.
“We’ll be looking at a successor study to Up-LIFT which would look at safety and performance when used in the home.
“Without question, it’s important with spinal cord injury to be able to operate this technology, which is why we were keen to incorporate voice activation into the system. Both of our platforms can be programmed by the clinician, but in the future may be operated by and used by the injured with their voices.
“But very importantly, we do our best to connect as frequently as possible with people with injury to inform the design of our product platforms, and inform our future direction as a company.
“We consider ourselves part of the community, so that feedback to ensure the design of our technologies is really usable and accessible, in my view, is vitally important.”
And with such huge advances and new-found hope for the future, many conversations have turned to whether SCI may be curable.
“I wouldn’t rule anything out, with human ingenuity and so forth, but what I would say is more realistic at this point is to have optimism – quite a bit of optimism – that movement and strength and function can improve, and in some cases, be restored with the benefit of therapies like ours,” says Dave.
“Perhaps other therapies and technologies will emerge, if you look at how far we have come. But for us, our vision is to support the SCI community around the world through our therapies, and we’ll continue to do that.
“We’re making steady progress across all areas of our plan, and while what we’re doing is difficult and complex, I’m confident we will come through.”
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