Gene therapy that inhibits targeted nerve cell signalling has effectively reduced neuropathic pain in trials, giving hope for a potential new treatment for a condition that can affect more than half of people living with spinal cord injury (SCI).
An international team of researchers found that the approach gave no detectable side effects in mice with spinal cord or peripheral nerve injuries.
Neuropathy involves damage or dysfunction in nerves elsewhere in the body, typically resulting in chronic or debilitating numbness, tingling, muscle weakness and pain.
There are no singularly effective remedies for neuropathy, the impact of which can have significant consequences mentally as well as physically.
Pharmaceutical therapies, for example, often require complex, continuous delivery of drugs and are associated with undesirable side effects, such as sedation and motor weakness. Opioids can be effective, but can also lead to increased tolerance and risk of misuse or abuse.
“One of the prerequisites of a clinically acceptable antinociceptive (pain-blocking) therapy is minimal or no side effects like muscle weakness, general sedation or development of tolerance for the treatment,” said senior author Dr Martin Marsala, professor in the Department of Anesthesiology in the UC San Diego School of Medicine.
“A single treatment invention that provides long-lasting therapeutic effect is also highly desirable. These finding suggest a path forward on both.”
Because clinicians and researchers are able to pinpoint the precise location of a spinal cord injury and origin of neuropathic pain, this has given rise to focus on developing treatments that selectively target impaired or damaged neurons in the affected spinal segments.
In recent years, gene therapy has proven an increasingly attractive possibility.
In the latest study, led by scientists at the University of California San Diego School of Medicine, researchers injected a harmless adeno-associated virus carrying a pair of transgenes that encode for gamma-aminobutyric acid or GABA into mice with sciatic nerve injuries and consequential neuropathic pain. GABA is a neurotransmitter that blocks impulses between nerve cells; in this case, pain signals.
The delivery and expression of the transgenes — GAD65 and VGAT — was restricted to the area of sciatic nerve injury in the mice and, as a result, there were no detectable side effects, such as motor weakness or loss of normal sensation.
The production of GABA by the transgenes resulted in measurable inhibition of pain-signaling neurons in the mice, which persisted for at least 2.5 months after treatment.
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.”
Walton Centre secures Centre of Excellence spinal status
Trust wins recognition for its work in fully endoscopic spinal surgery
The Walton Centre NHS Foundation Trust has received Centre of Excellence status for its work in fully endoscopic spinal surgery.
The award, given by RIWOspine, the manufacturers of the innovative fully endoscopic equipment, comes after the Trust’s charity funded the project in 2020.
The procedure is used to treat spinal conditions such as sciatica due to disc bulges and spinal stenosis, along with other ever evolving newer surgical indications.
As part of the recovery process for some of the procedures, patients can be up and walking around merely hours after the surgery. In many cases, patients can go home the same day if they have recovered enough.
Gaining Centre of Excellence is a gold standard, making the hospital one of only a handful to achieve the status, and comes in recognition of its work with patients across the wide geographical areas of Cheshire, Merseyside and North Wales. It is the latest innovation to be offered by The Walton Centre, the UK’s only dedicated specialist neuro NHS Trust.
Consultant spinal surgeon Mr Narendra Rath, one of few surgeons in the country who can perform this type of surgery, said: “I am delighted and so proud of the team here at The Walton Centre.
“It’s been an extraordinary two years, but the team has worked hard to bring this service to patients who need it.
“Fully endoscopic spinal surgery has provided us with skills to tackle spinal problems in various ways and it is not only about discectomy procedures.
“Being keyhole, the procedure causes minimal tissue damage and can improve patient rehabilitation. It’s a pioneering branch of spinal surgery, practiced in only few centres across the world, and has a potential to transform future spinal surgery.”
One patient, 26-year-old Ciaran Rooney from Wirral, started to have trouble with his back a couple of years ago.
Mr Rath operated on Ciaran towards the end of last year and he was able to go home the same day.
“Mr Rath assessed and got me in for the operation quickly. Before that I was in an incredible amount of pain, I was limping it was that severe,” recalls Ciaran.
“Hours after the procedure the team got me up and about walking to see the progress I was making.
“I couldn’t believe it and I feel so lucky to have had the surgery, it’s got me back on my feet – literally!”
The innovative endoscopic equipment, made by RIWOspine, involves keyhole technology, which allows the Trust to deliver precision spinal procedures.
The tools are paired wirelessly with high definition 4K monitors to enable safe procedures with minimal invasion, which may reduce the length of time patients need to recover in hospital.
The funding of this technology was made possible thanks to a significant legacy left to The Walton Centre Charity in 2019.
Andy Singh, head of RIWOspine UK, said: “We are very pleased to announce this Centre of Excellence award for The Walton Centre.
“The staff at the hospital have worked closely with us, and their hard work and professionalism has resulted in this award.
“This latest generation of full endoscopic spine surgery, allowing the interlaminar surgical approach has meant many more patient pathologies have been treatable, where once, these patients required open surgery.”
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