Researchers in the United States have developed an injectable therapy that harnesses ‘dancing molecules’ to repair tissue after severe spinal cord injuries, which is said to have the potential to cure paralysis.
In a new study, researchers at Northwestern University administered a single injection to tissues surrounding the spinal cords of paralysed mice.
Just four weeks later, the animals regained the ability to walk.
By sending bioactive signals to trigger cells to repair and regenerate, the breakthrough therapy dramatically improved severely injured spinal cords in five key ways:
- The severed extensions of neurons, called axons, regenerated;
- scar tissue, which can create a physical barrier to regeneration and repair, significantly diminished;
- myelin, the insulating layer of axons that is important in transmitting electrical signals efficiently, reformed around cells;
- functional blood vessels formed to deliver nutrients to cells at the injury site;
- more motor neurons survived.
After the therapy performs its function, the materials biodegrade into nutrients for the cells within 12 weeks and then completely disappear from the body without noticeable side effects.
This is the first study in which researchers controlled the collective motion of molecules through changes in chemical structure to increase a therapeutic’s efficacy.
“Our research aims to find a therapy that can prevent individuals from becoming paralyzed after major trauma or disease,” said Northwestern’s Samuel I. Stupp, who led the study.
“For decades, this has remained a major challenge for scientists because our body’s central nervous system, which includes the brain and spinal cord, does not have any significant capacity to repair itself after injury or after the onset of a degenerative disease.
“We are going straight to the FDA to start the process of getting this new therapy approved for use in human patients, who currently have very few treatment options.”
According to the National Spinal Cord Injury Statistical Center, nearly 300,000 people are currently living with a spinal cord injury in the United States.
Less than three per cent of people with complete injury ever recover basic physical functions, and approximately 30 per cent are re-hospitalised at least once during any given year after the initial injury, incurring significant lifetime health care costs per patient.
“Currently, there are no therapeutics that trigger spinal cord regeneration,” said Stupp, an expert in regenerative medicine.
“I wanted to make a difference on the outcomes of spinal cord injury and to tackle this problem, given the tremendous impact it could have on the lives of patients.
“Also, new science to address spinal cord injury could have impact on strategies for neurodegenerative diseases and stroke.”
The science behind Stupp’s new breakthrough therapeutic is tuning the motion of molecules, so they can find and properly engage constantly moving cellular receptors.
Injected as a liquid, the therapy immediately gels into a complex network of nanofibres that mimic the extracellular matrix of the spinal cord.
By matching the matrix’s structure, mimicking the motion of biological molecules and incorporating signals for receptors, the synthetic materials are able to communicate with cells.
“Receptors in neurons and other cells constantly move around,” Stupp said. “The key innovation in our research, which has never been done before, is to control the collective motion of more than 100,000 molecules within our nanofibres.
“By making the molecules move, ‘dance’ or even leap temporarily out of these structures, known as supramolecular polymers, they are able to connect more effectively with receptors.”
While the new therapy could be used to prevent paralysis after major trauma as well as from diseases, Stupp believes the underlying discovery — that “supramolecular motion” is a key factor in bioactivity — can be applied to other therapies and targets.
“The central nervous system tissues we have successfully regenerated in the injured spinal cord are similar to those in the brain affected by stroke and neurodegenerative diseases, such as ALS, Parkinson’s disease and Alzheimer’s disease,” Stupp said.
“Beyond that, our fundamental discovery about controlling the motion of molecular assemblies to enhance cell signalling could be applied universally across biomedical targets.”
ONWARD makes first human implant of new technology
Trials of its implantable pulse generator (IPG) and HemON study are stepping up efforts to support people living with spinal cord injury
The first in-human use of an implantable pulse generator (IPG) has been made by ONWARD, stepping up its efforts to help change the futures for people with spinal cord injury (SCI).
The ARC IM IPG is designed to stimulate the spinal cord to restore movement and autonomic function for people with SCI and other conditions that impact mobility.
Its implantation into a human for the first time marks the start of patient enrolment in ONWARD’s HemON Study, which aims to enrol up to 16 participants at Switzerland’s Lausanne University Hospital (CHUV), to evaluate the safety and preliminary efficacy of ARC IM therapy to improve blood pressure management and trunk control in people with SCI.
Orthostatic hypotension affects around 75 per cent of people with SCI, and is characterised by debilitatingly low blood pressure that may occur when people sit upright, stand, or change body position.
“ONWARD’s ARC IM IPG offers surgeons precision and flexibility never before available in an implantable neurostimulator,” said Dr Jocelyne Bloch, chief of functional neurosurgery at CHUV.
“Clinicians will be able to leverage these advanced capabilities to refine and deliver epidural stimulation therapies for people with spinal cord injury.”
The IPG and HemON Study build further on the progress of ONWARD in giving hope to people with SCI, with its STIMO-BRIDGE study showing the potential of its ARC IM technology through enabling paralysed people to regain the ability to walk, stand, swim and cycle, supported by intense rehabilitation.
Its Up-LIFT study, involving 14 leading SCI sites across the UK, United States, Canada and the Netherlands, is gathering the data to prove the efficacy of its ARC EX technology.
The ONWARD ARC IM IPG was purpose-designed to deliver targeted electrical stimulation to the spinal cord in the precise areas responsible for triggering or controlling movement and autonomic functions that may be affected by a spinal cord injury or neurodegenerative disorder.
The IPG is designed to operate in closed-loop, incorporating data from sensors or other devices that may be deployed inside or outside the body.
It is also designed to deliver therapy through an associated ARC IM lead with precision and flexibility, allowing clinicians to apply biomimetic stimulation that can closely replicate normal spinal cord activity patterns during mobility or autonomic function.
“The first implant of our ARC IM IPG is a huge milestone for ONWARD and the SCI community,” said Dave Marver, CEO of ONWARD.
“This important achievement validates our vision for a future in which clinicians will no longer need to struggle with modified pain stimulators to explore new treatments and instead will be able to use devices and therapies designed specifically to treat people with spinal cord injury and their unique needs.”
Sports stars support Wings for Life World Run
The event, uniting teams of runners globally, raises money for spinal cord research by Wings for Life Foundation
Internationally-known athletes and sports teams are spearheading the charge to secure teams of runners from around the world to take part in an event to raise vital funds for spinal cord research.
The Wings for Life World Run brings together people from around the world for an event on Sunday (May 8), where they all join together – physically or virtually, through use of an app – in support of the quest to find a cure for spinal cord injury.
More than 8,000 teams globally have already signed up for the run, with world-class athletes and teams also committing their support.
Liverpool and England footballer Trent Alexander-Arnold has committed his support to the Wings for Life World Run.
Although his playing schedule and Liverpool’s title challenge prevents him from taking part on the day, he urged others to show their support for the work of the Wings for Life Foundation, whose purpose is to find a cure for spinal cord injury, an area where a huge amount of progress is being achieved globally.
“After meeting Emerson Grant in 2019 I have wanted to work out ways to help raise awareness of Wings for Life,” he said.
“I want to get as many sign-ups for my team as possible to raise more money for Wings for Life to support their aim of finding a cure for spinal cord injury.”
Also throwing their support behind the Wings for Life World Run are two Formula-1 teams – Scuderia AlphaTauri and Oracle Red Bull Racing. The motorsport teams have been encouraging their large fan followings to sign up and take part in the global race for the good cause.
Two leading Greek athletes — Dimitris Kyrsanidis and Nikolas Plytas — and three Olympians from Norway – world record holder and Olympic gold medalist (110m hurdles) Karsten Warholm, double Olympic champion in cross-country skiing Petter Northug, and triathlete and Olympic champion Kristian Blummenfelt – will all be taking part.
German ultra runner and team captain Flo Neuschwander, who organised the largest team ever last year with 3,061 participants, is now looking to improve on his achievement.
“The Wings for Life World Run is a tremendous highlight for me every year. I feel like I’m always try to push myself beyond my limits in this event,” he said.
“In 2020, I managed to run the fastest pace ever in a race, even though I was running all by myself with the app.
“But to be honest my biggest goal at the Wings for Life World Run is to lead the biggest team again.
“Since 2016 the ‘Run with the Flow Team’ has been the winning team and last year we managed even to run 45,000 kilometers collectively, which means we actually ran one lap around the world together on race day.
“The more runners, the more donations – and that, along with being part of a super day of running, is the biggest goal for all of us who take part in this great event.”
The Wings for Life World Run enables people to run collectively, wherever they are in the world, at exactly the same time.
Participants run as far as possible until the Catcher Car passes them, with 100 per cent of the entry fee going into the work of the Wings for Life Foundation into spinal cord research.
For more information and registration, visit www.wingsforlifeworldrun.com.
Christopher & Dana Reeve Foundation appoint new senior figure
Dr Marco Baptista joins as chief scientific officer, moving from the Michael J. Fox Foundation
A leading figure in neuroscience has joined the Christopher & Dana Reeve Foundation to help lead its mission to advance cures for spinal cord injury (SCI) and paralysis.
Dr Marco Baptista joins as Chief Scientific Officer and will provide scientific and innovative oversight of the nonprofit’s collaborative approach to accelerating the field toward meaningful therapeutics.
Dr Baptista joins the Reeve Foundation as it celebrates 40 years of progress and the seismic shift that it helped steer to move the field of SCI research to its current fast-developing state.
To date, the Foundation has funded more than $140million of research around the world, uniting the brightest minds in the field to help usher a new era of scientific inquiry focused on developing and delivering treatments that are, today, pushing the world toward real cures.
“What began as a grassroots movement by pioneers who refused to accept the long-standing dogma that the spinal cord, once injured, could never be repaired is today an exciting field primed to cross the critical threshold of laboratory science to real-world therapies widely available to our community,” said Maggie Goldberg, President and CEO of the Reeve Foundation.
“Dr Baptista brings a special blend of neuroscience acumen to our organization, our research collaborative and the community of people living with or caring for someone with SCI. His strong industry knowledge will move us from the bench to the bedside. We’re honored to have him aboard.”
Dr Baptista joins the Reeve Foundation from the Michael J. Fox Foundation for Parkinson’s Research, where he served as Vice President of Research Programs.
In his decade with the Fox Foundation, he led priority research around LRRK2, a major genetic mutation that can increase the chances of developing Parkinson’s disease – an area of study that had also been the focus of his efforts in the pharmaceutical industry, where he spent five years working at Schering-Plough, and then Merck when it acquired the company in 2009.
“Joining the Reeve Foundation is a natural extension of my long and deep commitment both to studying the central nervous system and my desire to help people,” said Dr Baptista.
“With the Foundation’s reputation and impact in care and scientific research for those living with SCI, it’s an exciting place to be at the right moment in time.
“The Reeve Foundation took this field from obscurity to one of real promise. Now, thanks in part to its funding of basic research, we’ve generated a solid understanding of the biological mechanisms underlying SCI and paralysis, and the drive toward cures is not a hammer looking at all the world as a nail.
“Rather, we can identify the studies that stand the greatest chances of success, learn quickly from those that fail, and remove barriers to our greatest shared goal: long-awaited cures.”
In his new role, Dr Baptista will manage the Foundation’s research portfolio, which includes a number of high-profile endeavours with the potential to swiftly move the needle toward clinically approved and market-ready products. These include:
- The Big Idea, a groundbreaking study at the University of Louisville investigating epidural stimulation to dramatically improve quality of life through improved cardiovascular health, bladder control, and other autonomic functions – and voluntary movement, including the previously impossible task of walking over ground. The trial is on track to be fully enrolled this summer.
- Research-driven financial investments, such as a partnership with ONWARD, a Netherlands-based company that has developed breakthrough technology currently in global clinical trials that deliver targeted, programmed stimulation of the spinal cord to restore movement and other functions; and Axonis, an emerging biotech advancing breakthrough research to develop therapies for neurological disorders.
- A strategic partnership with the UK’s International Spinal Research Trust (ISRT) to co-develop a research strategy with a joint focus on chronic injury, combination approaches and clinical translation. At the core of the alliance is a collaborative blueprint that aims to establish a framework for decision-making, planning and governance to advance the most promising therapies from the preclinical stage through clinical trials and into medical practice. Most recently, the Reeve Foundation and ISRT announced joint funding for a newly created translational award totaling $1.3 million, focused on restoring function in chronic SCI through novel circuit formation.
- Support for the North American Clinical Trials Network (NACTN), a research network established by the Foundation that to date has enrolled more than 1000 subjects to a data registry; it also actively collaborates with other clinical trial networks in Europe and Canada. Dr. Baptista will liaise with the principal investigators leading this important, ongoing research.
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