Northwestern University scientists have developed the most advanced organoid model for human spinal cord injury to date.

In a new study, the research team used lab-grown human spinal cord organoids — miniature organs derived from stem cells — to model different types of spinal cord injuries and test a promising new regenerative therapy.

For the first time, the scientists demonstrated that human spinal cord organoids can accurately mimic the key effects of spinal cord injury, including cell death, inflammation and glial scarring, a dense mass of scar tissue that creates a physical and chemical barrier to nerve regeneration.

When treated with “dancing molecules” — a new therapy that reversed paralysis and repaired tissues in a previous animal study — the injured organoids showed significant outgrowth of neurites, the long extensions of neurons that connect the cells to one another. The glial scar-like tissues of treated injured organoids also significantly diminished. These results give researchers further hope that the treatment, which recently earned an Orphan Drug Designation from the U.S. Food and Drug Administration (FDA), should improve outcomes for patients with spinal cord injuries.

The study was published today (Feb. 11) in the journal Nature Biomedical Engineering.

“One of the most exciting aspects of organoids is that we can use them to test new therapies in human tissue,” said Northwestern’s Samuel I. Stupp, the study’s senior author and inventor of dancing molecules. “Short of a clinical trial, it’s the only way you can achieve this objective. We decided to develop two different injury models in a human spinal cord organoid and test our therapy to see if the results resembled what we previously saw in the animal model. After applying our therapy, the glial scar faded significantly to become barely detectable, and we saw neurites growing, resembling the axon regeneration we saw in animals. This is validation that our therapy has a good chance of working in humans.”

A pioneer in self-assembling materials and regenerative medicine, Stupp is the Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern, where he has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences and Feinberg School of Medicine. He also directs the Center for Regenerative Nanomedicine (CRN). Nozomu Takata, a research assistant professor of medicine at Feinberg and member of CRN, is the paper’s first author.

Tiny organoid, giant advance

Grown in the lab from induced pluripotent stem cells, organoids are miniature, simplified versions of human organs. Although they are only partial organs, organoids mimic the tissue structure, cellular complexity and function of the real thing. This sophisticated mimicry makes organoids ideal for modeling human diseases, testing therapeutics and understanding organ development. Compared to testing treatments in animals and humans, testing in organoids is faster and much less expensive.

While other researchers have developed human organoids to investigate physiological aspects of the spinal cord, Stupp’s model represents a giant leap forward to find treatments for devastating, paralyzing human injuries. Measuring several millimeters in diameter, the organoids were large and mature enough to develop the injury model.

Stupp’s team grew the spinal cord organoids from stem cells over the course of months, allowing them to develop complex features including neurons and astrocytes. The team also was the first to add microglia — immune cells in the central nervous system — to simulate inflammatory responses to traumatic spinal cord injury.

“It’s kind of a pseudo-organ,” Stupp said. “We were the first to introduce microglia into a human spinal cord organoid, so that was a huge accomplishment. It means that our organoid has all the chemicals that the resident immune system produces in response to an injury. That makes it a more realistic, accurate model of spinal cord injury.”

What are ‘dancing molecules’?

After developing a mature spinal cord organoid, Stupp and his team wanted to examine the effects of injuries and subsequent treatment. First introduced in 2021, the dancing molecules therapy harnesses molecular motion to reverse paralysis and repair tissues after traumatic spinal cord injuries. It is part of the Stupp laboratory’s platform of supramolecular therapeutic peptides (STPs), technologies that use large assemblies of 100,000 or more molecules to activate cell receptors using the body’s own natural signals to regenerate and repair. (The concept of supramolecular therapies also is used in current GLP-1 drugs for weight loss and diabetes, an area that Stupp’s lab investigated nearly 15 years ago.)

Injected as a liquid, the dancing molecules therapy immediately gels into a complex network of nanofibers that mimic the extracellular matrix of the spinal cord. By fine-tuning the collective motion, or “dancing,” of the molecules within the nanofibers, Stupp’s team found the therapy connects more effectively with constantly moving cellular receptors.

“Given that cells themselves and their receptors are in constant motion, you can imagine that molecules moving more rapidly would encounter these receptors more often,” Stupp said in 2021. “If the molecules are sluggish and not as ‘social,’ they may never come into contact with the cells.” 

In animal studies, a one-time injection administered 24 hours after severe injury helped mice regain the ability to walk in just four weeks. Compared to injections with slower-moving molecules, formulations with enhanced molecular motion had greater therapeutic efficacy, indicating increased bioactivity and cellular signaling.

Testing a breakthrough therapy

To model spinal cord injury, Stupp’s team induced two types of common injuries. The researchers cut some of the organoids with a scalpel to simulate a laceration, like a surgical wound. For other organoids, the researchers applied a compressive contusion injury to simulate wounds that might occur in a serious car accident or from a steep fall.

Both injuries caused cells to die and a glial scar to form — just like in a real spinal cord injury.

“We could distinguish between the astrocytes that are a part of normal tissue and the astrocytes in the glial scar, which are large and very densely packed,” Stupp said. “We also detected the production of chondroitin sulfate proteoglycans, which are molecules in the nervous system that respond to injury and disease.”

After simulating injuries, Stupp’s team tested the effectiveness of the dancing molecules. When applied to the injured organoids, the liquid therapy gelled to form a scaffold. The therapy calmed inflammation, reduced glial scarring, caused neurites to extend and encouraged neurons to grow in neat, organized patterns.

A type of neurite, called an axon, is often severed during spinal cord injury, disconnecting the communication network among neurons. That disconnection results in paralysis and a loss of sensation below the injury site. Regenerating neurites could reestablish these connections to prevent or reverse these devastating outcomes.

The miracle of motion

Stupp attributes the treatment’s success to its supramolecular motion — or the ability of the molecules to move rapidly or even temporarily leap out of the nanofibers. Testing the therapy on healthy organoids only confirmed Stupp’s hunch.

“Before we even developed the injury model, we tested the therapy on a healthy organoid,” he said. “The dancing molecules spun out all these long neurites on the surface of the organoid but, when we used molecules that had less or no motion, we saw nothing. This difference was very vivid.”

Next, Stupp’s team plans to build even more advanced organoids to further refine their model. They also plan to develop a human spinal cord organoid that models older, chronic injuries, which typically have more stubborn scar tissue. With further work, Stupp said his group’s mini spinal cords also could be used in personalized medicine, by creating implantable tissue using a patient’s own stem cells to avoid immune rejection.

The study, “Injury and therapy in the human spinal cord organoid,” was supported by the Center for Regenerative Nanomedicine at Northwestern University and a gift from the John Potocsnak Family for spinal cord injury research.

Source: Northwestern University

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“Astrocytes are critical responders to disease and disorders of the central nervous system — the brain and spinal cord,” said neuroscientist Joshua Burda, PhD, assistant professor of Biomedical Sciences and Neurology at Cedars-Sinai and senior author of the study. “We discovered that astrocytes far from the site of an injury actually help drive spinal cord repair. Our research also uncovered a mechanism used by these unique astrocytes to signal the immune system to clean up debris resulting from the injury, which is a critical step in the tissue-healing process.”

The team named these cells “lesion-remote astrocytes,” or LRAs. They also identified several distinct subtypes. For the first time, the study explains how one subtype can detect damage from a distance and respond in ways that support recovery.

How the Spinal Cord Responds to Injury

The spinal cord is a long bundle of nerve tissue that extends from the brain down the back. Its inner region, called gray matter, contains nerve cell bodies along with astrocytes. Surrounding that is white matter, made up of astrocytes and long nerve fibers that carry signals between the brain and the rest of the body. Astrocytes help maintain a stable environment so these signals can travel properly.

When the spinal cord is injured, nerve fibers are torn apart. This can cause paralysis and disrupt sensations such as touch and temperature. The damaged fibers break down into debris. In most tissues, inflammation remains confined to the injured area. In the spinal cord, however, nerve fibers can span long distances, so damage and inflammation can spread well beyond the original injury site.

Lesion-Remote Astrocytes and Immune Cleanup

In experiments involving mice with spinal cord injuries, researchers found that LRAs play a key role in promoting repair. They also found strong signs that the same process occurs in spinal cord tissue from human patients.

One LRA subtype produces a protein called CCN1. This molecule sends signals to immune cells known as microglia.

“One function of microglia is to serve as chief garbage collectors in the central nervous system,” Burda said. “After tissue damage, they eat up pieces of nerve fiber debris — which are very fatty and can cause them to get a kind of indigestion. Our experiments showed that astrocyte CCN1 signals the microglia to change their metabolism so they can better digest all that fat.”

According to Burda, this improved debris removal may help explain why some patients experience partial, spontaneous recovery after spinal cord injury. When researchers eliminated astrocyte-derived CCN1, healing was significantly reduced.

“If we remove astrocyte CCN1, the microglia eat, but they don’t digest. They call in more microglia, which also eat but don’t digest,” Burda said. “Big clusters of debris-filled microglia form, heightening inflammation up and down the spinal cord. And when that happens, the tissue doesn’t repair as well.”

Implications for Multiple Sclerosis and Brain Injury

When scientists examined spinal cord samples from people with multiple sclerosis, they observed the same CCN1-related repair process. Burda noted that these basic repair principles may apply broadly to injuries affecting either the brain or spinal cord.

“The role of astrocytes in central nervous system healing is remarkably understudied,” said David Underhill, PhD, chair of the Department of Biomedical Sciences. “This work strongly suggests that lesion-remote astrocytes offer a viable path for limiting chronic inflammation, enhancing functionally meaningful regeneration, and promoting neurological recovery after brain and spinal cord injury and in disease.”

Burda is now working to develop strategies that harness the CCN1 pathway to improve spinal cord healing. His team is also studying how astrocyte CCN1 may influence inflammatory neurodegenerative diseases and aging.

Source: Cedars-Sinai Medical Center

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Onward Medical has secured the CE mark in Europe for ARC-EX, a system to support the restoration of movement and function in individuals with spinal cord injury (SCI).

Secured under the European Union’s Medical Device Regulation (EU MDR), ARC-EX delivers electrical spinal cord stimulation (SCS) for SCI via electrodes attached to the neck, presenting a non-invasive option.

The Netherlands-headquartered company’s ARC-EX is the first SCI-approved device in Europe that is specifically indicated for improving hand strength and sensation in adults with SCI and is promoted for use in conjunction with standard rehabilitation practices. It joins other SCIs on the European market, including Aneuvo’s ExaStim, which is indicated for restoring motor function in individuals with chronic SCI.

According to the World Health Organization (WHO), SCI affects around seven million people worldwide, with an estimated 300,000 in the US.

Onward said a phased roll-out of ARC-EX in Europe will be initiated in the coming weeks, starting with Germany, with other countries to follow “as soon as possible” thereafter.

Onward’s CEO Dave Marner commented: “Hand sensation and strength is a primary recovery target after SCI. The ARC-EX Therapy opens new doors for the SCI community in Europe, offering opportunities for recovery and care that were previously unavailable.”

European approval for ARC-EX follows Onward’s receipt of de novo classification for the system from the US Food and Drug Administration (FDA) in December 2024.

Both approvals were supported by Onward’s pivotal Up-LIFT (NCT04697472) trial, in which the system met its primary and secondary endpoints in May 2024. Published in Nature Medicine, the trial results demonstrated that 90% of patients who used the treatment improved strength or function, with 87% reporting quality of life (QoL) improvement.

Other study findings included reports of less spasm frequency, improved sleep quality, and improved upper body sensation and sense of touch. Onward also highlighted that benefits were observed in patients with injuries incurred up to 34 years ago.

According to a report by GlobalData, Onward has nine other neurology devices in active stages of development, including ARC-IM, an implantable system designed to address several unmet needs, including blood pressure instability after spinal cord injury.

Source: Medical Device Network

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What if we could restore the ability to walk to people paralyzed by injury or illness? This vision is now moving closer to reality. Three years ago, Tel Aviv University researchers succeeded in engineering a human spinal cord in the lab for the first time. Since then, progress has been rapid, with animal trials showing unprecedented success. Now, for the first time, the technology is set to be tested in human patients.

Prof. Tal Dvir, of TAU’s Sagol Center for Regenerative Biotechnology, head of the Nanotechnology Center, and Chief Scientist of the biotech company Matricelf, explains:
“The spinal cord is made up of nerve cells that transmit electrical signals from the brain to every part of the body. When the spinal cord is torn due to trauma — from a car accident, a fall, or a battlefield injury — this chain is broken. Think of it like an electrical cable that’s been cut: if the two parts don’t touch, the electrical signal can’t pass. The cable won’t carry electricity, and in the same way, the person can’t transmit the signal beyond the site of the injury.”

This is one of the few injuries in the human body with no natural ability to regenerate. “Neurons are cells that do not divide and do not renew themselves. They are not like skin cells, which can repair themselves after injury. They are more similar to heart cells: once damage occurs, the body cannot restore them,” notes Prof. Dvir.

Engineering a Personalized Implant

To overcome this challenge, the TAU researchers developed a fully personalized process. Blood cells are taken from the patient and reprogrammed through genetic engineering to behave like embryonic stem cells, capable of becoming any type of cell in the body.

Meanwhile, fat tissue from the same patient is used to extract substances such as collagen and sugars. These are used to produce a unique hydrogel. “The beauty of this gel is that it’s also personalized, just like the cells. We take the cells that we’ve reprogrammed into embryonic-like stem cells, place them inside the gel, and mimic the embryonic development of the spinal cord,” says Prof. Dvir.

The result is a complete three-dimensional implant. “At the end of the process, we don’t just turn the cells into motor neurons — because cells alone won’t help us — but into three-dimensional tissue: neuronal networks of the spinal cord. After about a month, we obtain a 3D implant with many neurons that transmit electrical signals. These 3D tissues are then implanted into the damaged area.”

From Animals to Human Patients

The researchers first tested the implant in lab animals. “We showed that we can treat animals with chronic injuries. Not animals that were injured just recently, but those we allowed enough time to pass — like a person more than a year after an injury. More than 80% of the animals regained full walking ability,” Prof. Dvir explains.

Encouraged by these results, the team submitted the findings to Israel’s Ministry of Health. “About six months ago we received preliminary approval to begin compassionate-use trials with eight patients. We decided, of course, that the first patient would be Israeli. This is undoubtedly a matter of national pride. The technology was developed here in Israel, at Tel Aviv University and at Matricelf, and from the very beginning it was clear to us that the first-ever surgery would be performed in Israel, with an Israeli patient.” he says.

Looking Ahead

The first implant in a human patient is expected within about a year. For the initial trials, the team will focus on patients whose paralysis is relatively recent — within about a year of injury. “Once we prove that the treatment works — everything is open, and we’ll be able to treat any injury,” says Prof. Dvir.

Behind the initiative are key figures from both academia and industry. Prof. Dvir founded Matricelf in 2019 together with Dr. Alon Sinai, based on the revolutionary organ engineering technology developed at TAU under a licensing agreement through Ramot, the University’s technology transfer company. The company’s CEO is Gil Hakim, while the scientific development is led by Dr. Tamar Harel-Adar and her team.

“They managed to get us to the stage of regulatory approvals so quickly — and that’s amazing,” says Prof. Dvir.

Gil Hakim, CEO of Matricelf , concludes: “This milestone marks the shift from pioneering research to patient treatment. For the first time, we are translating years of successful preclinical work into a procedure for people living with paralysis. Our approach, using each patient’s own cells to engineer a new spinal cord, eliminates key safety risks and positions Matricelf at the forefront of regenerative medicine. If successful, this therapy has the potential to define a new standard of care in spinal cord repair, addressing a multi-billion-dollar market with no effective solutions today. This first procedure is more than a scientific breakthrough, it is a value-inflection point for Matricelf and a step toward transforming an area of medicine long considered untreatable. We are proud that Israel is leading this global effort and are fully committed to bringing this innovation to patients worldwide.”

Source: Tel Aviv University

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A Phase 1 human clinical trial to treat chronic spinal cord injury, the first of its kind in the world, has commenced to test the efficacy and safety of a revolutionary new treatment using nasal cells.

The Griffith University trial has been three decades in the making and involves taking olfactory ensheathing cells, which are specialised cells involved in our sense of smell, from the nose as they have numerous therapeutic properties for repairing and regenerating nerves.

Lead researcher Professor James St John, Head of Griffith’s Clem Jones Centre for Neurobiology and Stem Cell Research and Principal Researcher at the Institute for Biomedicine and Glycomics, is carrying on the legacy of the late Professor Emeritus Alan Mackay-Sim AM.

“Once the cells have been removed from the patient’s nose, they are then used to create an innovative nerve bridge which is about the size of a very small worm,” Professor St John said.

“The nerve bridge is then implanted into the spine at the site of the injury, offering what we think is the best hope for treating spinal cord injury.

“To help stimulate regeneration, patients will undergo intensive rehabilitation for three months prior to the transplantation and then for eight months after the transplantation.

“While primary assessments are to ensure the therapy is safe, we will also be measuring numerous aspects to assess if there are changes in functional outcomes that are important to people living with spinal cord injury.

“The ability to regain some sense of function, whether it’s regaining independent function of their bladder or bowel, regaining movement in their fingers, or the ability to stand and hug a loved one again can improve quality of life.

“Regaining some form of independence can open the world up to people living with a chronic acquired spinal injury.”

The trial, to be conducted at Gold Coast University Hospital, is a blinded and randomised control study with preclinical research demonstrating the olfactory nerve bridges are effective in repairing spinal cord injury in animal models.

CEO of the Clem Jones Foundation, Peter Johnstone, said the latest milestone illustrated how long-term philanthropic support could foster ground-breaking research with the potential to change lives for the better. 

“The Clem Jones Foundation has supported this world-leading project from day one alongside other philanthropic groups and individuals which meant it also attracted state and federal government funding commitments,” Mr Johnstone said. 

“All of the funding partners recognise that results from medical research never happen overnight but rely on long-term funding as well as the long-term application of the knowledge, skills, and hard work of the talented team of researchers at Griffith University.”

Founder of the Perry Cross Spinal Research Foundation, Perry Cross AM, who became a ventilated quadriplegic at age 19 from a rugby accident, has dedicated his life to advocating for a cure.

“This clinical trial represents a long-awaited breakthrough that speaks to the enduring strength of those impacted by spinal cord injury and the extraordinary belief of those who support us,” Mr Cross said.

“For too long, individuals living with paralysis have been told that recovery lies beyond the horizon of possibility.

“Today, we challenge that notion with evidence, ambition and above all, hope.

“It is proof that philanthropy, when guided by purpose and vision, can accelerate real change. Every contribution has mattered, and each gesture of support has brought us closer to this point.

“For someone like me, who knows all too well the permanence of spinal cord injury, this trial offers not just the possibility of improved function, but a renewed sense of independence and dignity; qualities that define the human experience.”

Professor St John said: “To have a cell transplantation therapy progressing to clinical trial after only eight years is testament to the benefits of the strategic translational research program the team has used.

“To be able to develop the therapy in Queensland is thanks to the incredible support from our funding partners, in particular the Motor Accident Insurance Commission as the major funder, the Clem Jones Foundation, the Perry Cross Spinal Research Foundation, National Health and Medical Research Council, Medical Research Future Fund, and the dedicated spinal injury community which has been the inspiration and driving force behind the therapy development.”

The trial is funded by the Medical Research Future Fund, Perry Cross Spinal Research Foundation, The Clem Jones Foundation, Queensland Government, Nicola and Andrew Forrest, Brazil Family Foundation, Terry and Rhonda White, and Griffith University.

Source: Griffith University

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A big change in how we treat spinal injuries is now possible, with the world’s first treatment that helps the body grow new cells getting approved for testing on people. This is a huge moment that could successfully treat something that, until now, couldn’t be fixed. Just this week, health groups in the US and China gave the green light for this worldwide study to treat spinal cord injury (SCI), which affects over 15 million people around the globe. SCI can happen to anyone and often comes from car accidents, sports injuries, serious falls, and workplace accidents. There’s no real cure; doctors mostly try to manage the pain and help people get some movement back with surgery and rehab. But people often end up unable to move or with serious problems for life.

Now, a Chinese company called XellSmart might change this forever. Their treatment uses special “young” cells that can turn into any kind of cell. Both the US and Chinese health groups have approved this treatment to start human testing. These young cells can become the kind of cells needed to replace the damaged parts of the spinal cord. The treatment aims to not just fix the injury but also help all the necessary cells grow back so the damaged area can work again.

XellSmart said that each year, about 100,000 people in China and 18,000 in the US get new, serious spinal cord injuries. This means almost 10 new cases every hour in China and two every hour in the US. Most of these patients end up with lasting problems that greatly affect their lives. Because the central nervous system doesn’t heal easily, fixing nerves after an SCI has been very hard.

This news about testing on humans comes after four years of research. The treatment is designed to be a “one-size-fits-all” solution that doesn’t need cells taken from the patient. This means, if it works in the trials, it will be easy to make a lot of it and get it to many people. Also, because these cells come from other sources, not the patient’s own body, and have been well-researched, there’s a low chance the body will reject them.

The SCI trial is being done with a hospital in China that is very good at treating these complicated spinal injuries. This is just the latest trial for XellSmart, which is also testing treatments for Parkinson’s disease and ALS. If the SCI trial works and this new treatment becomes available, it has amazing potential, including helping people who can’t move regain function.

Realistically, this first test, which checks how safe the treatment is, how well it works, and what the right amount to give is, should be done by next year. If it’s successful, it will move to the next stage with more people. That second stage would likely start in 2028 at the earliest. But then, this treatment could be made in large amounts and be “off the shelf” within five to seven years. A spokesperson for XellSmart said, “We’re moving beyond just caring for people and into curing them. For the first time, we’re giving real hope to millions living with spinal cord injury.”

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In this study, published in the prestigious journal Nature on May 21, individuals with incomplete spinal cord injury safely received a combination of stimulation of a nerve in the neck with progressive, individualized rehabilitation.

This approach, called closed-loop vagus nerve stimulation (CLV), produced meaningful improvements in arm and hand function in these individuals.

The unprecedented results position the UT Dallas scientists to proceed with a pivotal trial — the final hurdle on the road to potential Food and Drug Administration (FDA) approval of vagus nerve stimulation for treatment of upper-limb impairment due to spinal cord injury.

This approach is based on over a decade of neuroscience and bioengineering efforts by investigators at UT Dallas. The therapy uses electrical pulses sent to the brain via a tiny device implanted in the neck and timed to occur during rehabilitative exercises. 

Previous work by UT Dallas researchers has demonstrated that stimulating the vagus nerve during physical therapy can rewire areas of the brain damaged by stroke and lead to improved recovery.

Dr. Michael Kilgard, the Margaret Fonde Jonsson Professor of neuroscience in the School of Behavioral and Brain Sciences and corresponding author, explained that treating spinal cord injury with CLV is different than conditions targeted in earlier studies.

“In stroke, people who do only therapy may get better, and adding CLV multiplies that improvement,” he said. “This study is different: Therapy alone for spinal cord injury didn’t help our participants at all.”

The trial involved 19 participants with chronic, incomplete cervical spinal cord injury. Each person performed 12 weeks of therapy, playing simple video games to trigger specific upper-limb movements. The implant was activated upon successful movements, resulting in significant benefits for arm and hand strength.

“These activities allow patients to regain strength, speed, range of motion and hand function. They simplify daily living,” said Dr. Robert Rennaker, professor of neuroscience and the Texas Instruments Distinguished Chair in Bioengineering, who designed the miniature implanted CLV device.

The study served as both a Phase 1 and Phase 2 clinical trial and included randomized placebo control in its first phase, in which nine of the 19 participants received sham stimulation rather than active treatment during the first 18 therapy sessions, then received CLV in the latter 18 sessions.

The participants ranged in age from 21 to 65 and were from one to 45 years post-injury. Neither of those factors, nor the severity of the impairment in those with any hand movement, influenced the degree of response to treatment.

“This approach produces results regardless of these factors, which often cause significant differences in success rates of other types of treatment,” said study co-author Dr. Jane Wigginton, medical doctor and chief medical officer at TxBDC, co-director of UTD’s Clinical and Translational Research Center, and medical science research director at the Center for BrainHealth.

“It is remarkable from a medical standpoint,” said Wigginton, who planned the clinical interactions and patient protections for the trial.

TxBDC has worked to treat a wide variety of conditions using CLV across 13 years of research. As a result, the FDA has approved vagus nerve stimulation for treating impaired upper-limb movement in stroke patients.

Wigginton said the latest results are especially exciting because they help people for whom there is no existing solution.

“The people in this study have now gained the ability to do things that are meaningful for them and impactful in their lives.”

The newest generation of the implantable CLV device, designed by Rennaker, is approximately 50 times smaller than their version from three years ago. It does not prevent patients from receiving MRIs, CT scans or ultrasounds.

A Phase 3 pivotal trial will include 70 participants at multiple U.S. institutions that specialize in spinal cord injury.

Co-author Dr. Seth Hays, associate professor of bioengineering and Fellow, Eugene McDermott Distinguished Professor in the Erik Jonsson School of Engineering and Computer Science, has been with the CLV project dating back to the earliest studies.

“Prior to this study, no person with spinal cord injury had ever received CLV,” he said. “This is the first evidence that gains can be made. Now we will set about determining how we make this optimally effective.”

Hays cautioned that it is not a foregone conclusion that the therapy will make it to patients after the next trial.

“We still have a long road ahead. For many reasons — financial, regulatory or scientific — this could still die on the vine,” he said. “But we have positioned ourselves to succeed.”

The research team emphasized the importance of the dozens of people involved in the work — both the patients and TxBDC’s partners at Baylor University Medical Center, Baylor Scott & White Research Institute and Baylor Scott & White Institute for Rehabilitation.

“This has been the hardest working, most altruistic group of professionals, and that has been incredibly impactful,” Wigginton said.

Noting that even outpatient surgery is complex for those with impaired mobility, Rennaker added, “These patients said, ‘Put that device in me’ — that’s a huge commitment. They deserve credit for paving the path for others.”

Other UTD-affiliated co-authors included Joseph Epperson BS’20, PhD’24, TxBDC research associate; cognition and neuroscience doctoral student Emmanuel Adehunoluwa MS’23; Amy Porter MBA’20, TxBDC director of operations; Holle Carey Gallaway MBA’23, TxBDC research biomedical engineer; and David Pruitt MS’14, PhD’16.

Kilgard has a financial interest in MicroTransponder Inc., which markets vagus nerve stimulation therapy for stroke. Rennaker is the founder and CEO of XNerve, which developed the device used in this study.

Funding: The research was funded by a grant (N66001-17-2-4011) from the Defense Advanced Research Projects Agency (DARPA), an agency of the Department of Defense, as well as the Wings for Life Accelerated Translational Program.

Source: Neuroscience News

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A brain wave decoder shows promise in using electrical stimulation to the spine to cue leg movement, researchers say.

The decoder could one day help restore mobility in people with spinal cord injuries.

Tests in 17 people without a spinal cord injury showed that the decoder could cue movement in their lower legs using spinal cord stimulation, researchers reported in the Journal of NeuroEngineering and Rehabilitation.

Participants wore a special cap fitted with electrodes that measured their brain activity, and were asked to either extend their leg at the knee or only think about the motion.

The recorded brain waves were then fed into the decoder so it could learn how people’s brains responded in both circumstances, researchers said.

As it happens, the actual and imagined movements used similar brain waves, researchers found.

“After we give the decoder this data, it learns to predict based on neural activity whenever there is movement or no movement,” senior researcher Ismael Seáñez, an assistant professor of biomedical engineering at Washington University in St. Louis, said in a news release. 

“We show that we can predict whenever someone is thinking about moving their leg, even if their leg does not actually move,” Seáñez said.

Using those brain waves, people were able to move their lower leg by just thinking about it, with an external electrode stimulating their spinal cord into producing the movement, researchers reported.

The study is a first step toward developing a brain-spine interface that uses real-time brain waves and spinal cord stimulation to promote movement in people with a spinal cord injury, researchers said.

The team next plans to see if these brain waves can be generalized. If so, a universal decoder could be implemented to help restore movement, rather than having to teach the device based on each person’s brain waves.

Source: Washington University in St. Louis

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Capitalizing on the flexibility of tiny cells inside the body’s smallest blood vessels may be a powerful spinal cord repair strategy, new research suggests.

In mouse experiments, scientists introduced a specific type of recombinant protein to the site of a spinal cord injury where these cells, called pericytes, had flooded the lesion zone. Once exposed to this protein, results showed, pericytes change shape and inhibit the production of some molecules while secreting others, creating “cellular bridges” that support regeneration of axons – the long, slender extensions of nerve cell bodies that transmit messages.

Researchers observed axon regrowth in injured mice that received a single treatment injection of the growth-factor protein, and the animals also regained movement in their hind limbs. An experiment involving human cells suggests the results are not restricted to mice.

“There’s a lot more that can be learned and a lot that can be expanded, but the more we worked on this, the more stunned we really were by the potency of this single treatment and how effective it was,” said senior study author Andrea Tedeschi, associate professor of neuroscience in The Ohio State University College of Medicine. “This finding goes beyond spinal cord injury – it has implications in brain injury and stroke, and neurodegenerative diseases as well.”

The work underscores how important blood vessel restoration is to recovery of neurological function after a spinal cord injury, researchers said.

“Spinal cord injuries are severe not only because they prevent transmission of information across the site of the injury, but because all of the vasculature structure and function is also compromised,” said first study author Wenjing Sun, assistant professor of neuroscience at Ohio State. “Even if you are able to reestablish neuronal connectivity from one end to the other, the overall effect will still not be maximized unless you take care of everything else that falls apart.”

The study was published April 18 in the journal Molecular Therapy.

Previous research suggesting pericytes interfere with spinal cord injury recovery had led some scientists to recommend clearing them from the lesion site to aid repair. But cancer research has indicated pericytes’ properties change when they’re exposed to a protein called platelet-derived growth factor BB (PDGF-BB) – which is one way tumors generate their own blood supply. In cancer, the aim is to block PDGF-BB signaling.

Earlier neuroscience research also indicated that pericytes are highly “plastic,” meaning they are very responsive to changes in the microenvironment – including the presence of PDGF-BB. Tedeschi and colleagues saw potential to harness that cell-protein relationship to stabilize the vasculature surrounding a spinal cord injury. In the process, they found the newly sprouted blood vessels established a pathway for regenerated axons to follow.

Starting with imaging studies, the team showed that when a spinal cord is severed, pericytes migrate into the injury site over time but don’t promote growth of functional blood vessels that are needed to support axon regeneration.

In cell-culture experiments, the researchers established a “carpet” of pericytes, added PDGF-BB, and then placed a layer of adult mouse sensory neurons on top and evaluated how much axons grew in 24 hours. The treated axons grew nearly as much as healthy axons extend under normal conditions.

PDGF-BB alone did not produce this result. Instead, experiments showed that pericytes combined with the growth factor rearranged fibronectin, a multifunctional adhesive glycoprotein that plays a critical role in tissue repair, cell attachment and motility. The cells themselves also change shape, becoming more elongated.

“We know these cells are going to infiltrate and deposit at the lesion epicenter. These elongated fiber structures that they become are far more permissive in promoting axons to regenerate from one end to the other and bypass the injury,” Tedeschi said.

“To extend the clinical relevance of our findings, we cultured mouse neurons on top of human pericytes that were exposed to PDGF-BB, and that was sufficient to trigger a growth-promoting effect, suggesting that this might really be a generalized phenomenon that is not restricted to mice.”

Turning to experiments in animals with spinal cord injury, researchers waited for seven days after the injury – the equivalent of about nine months in a human adult – before injecting a single dose of PDGF-BB at the injury site. Analysis of tissue four weeks after the injury showed that the PDGF-BB injection produced robust axon regenerative growth compared to the axon response in injured control mice.

“When we looked at formation of these pericyte structures that crossed the injury site, we saw the treatment promoted the growth of these bridges. And most if not all of these regenerating axons were able to escape the injury site by riding these cellular bridges that have formed in response to PDGF-BB administration,” Sun said.

Electrophysiological and movement assessments of injured animals treated with PDGF-BB detected sensory activity beyond the lesion site and showed the mice regained better control of their hind limbs compared to control mice. The animals also were less sensitive to a non-painful stimulus, suggesting they did not experience the neuropathic pain that is often triggered by a spinal cord injury.

Analysis of the presence of inflammatory proteins during the repair process suggested that PDGF-BB administration not only promotes axon regeneration, but also reduces inflammation. RNA sequencing showed that spinal cord injury led to decreased gene expression by pericytes, but that the cells retained their core properties and did not convert into a different kind of cell – for example, a cell type that could end up being destructive to the injury environment.

“There was a decrease in some classical pericyte markers, but a gain of some additional function linked to the attempt to rebuild cellular bridges and functional vessels,” Sun said. “From the overall gene signature in our data, they’re still classified as a pericyte.”

Because Tedeschi, Sun and colleagues have previously shown in mice that gabapentin promotes regeneration of neural circuits after spinal cord injury, there’s potential to consider a multipronged approach to therapy, Sun said.

“We could combine both – modulating intrinsic properties of adult neurons with a drug, and what we are doing here, modulating the non-neuronal environment to produce cellular interactions that provide a more permissive substrate for the neuron to grow on,” she said.

More work is planned to determine the precise timing for administration of PDGF-BB – with the presumption that pericytes take some time to migrate to the injury – as well as the ideal concentration of the treatment and a potential time-released delivery system.

Source: Ohio State News

The post “Cellular Bridges” Help Repair Spinal Cord After Injury appeared first on Spinal Cord Injury Information Pages.

An estimated 18,000 people in the United States annually suffer from new injuries to their spinal cords. Unfortunately for those afflicted in such cases, no FDA-approved therapy is currently available. Scientists at UC San Diego are looking into the body’s healing mechanisms for clues on recovery from spinal cord injury.

A new study by researchers in the Department of Neurobiology (School of Biological Sciences) has uncovered a source of potential hope in the form of a gene that is known to be involved in key developmental processes in various tissues. Receptor tyrosine kinase, or “RYK,” has been previously associated with the regeneration of axons, the long, thin extensions of nerve cells that transmit impulses. However, RYK, the researchers found, is involved in many more functions.

Professor Yimin Zou and colleagues have published surprising results that reveal that RYK expression inhibits wound healing, offering implications for new treatments for paralysis after spinal cord injury.

“We did not know that RYK is a target to enhance wound healing,” said Zou. “Our discovery may give rise to much needed therapeutics to help the recovery of people who have spinal cord injury.”

Since there are no treatments, there is often danger following a spinal cord injury that secondary damage will grow and lead to chronic conditions. The body’s wound healing system, which is necessary to stop secondary injuries, involves a highly coordinated response of various cell types. These include astrocytes, which are cells in the central nervous system that support a broad range of functions.

Testing in mice confirmed that RYK is a major communication hub that coordinates how astrocytes respond to injury. RYK, they found, also regulates signals from astrocytes to other cell types. During experiments in which the RYK gene was blocked, or knocked out, recovery was accelerated. “Therefore RYK is a promising therapeutic target to accelerate wound healing, promote neuronal survival and connectivity and enhance functional recovery,” the researchers conclude in their paper.

“Astrocytic RYK signaling coordinates scarring and wound healing after spinal cord injury” was published April 10, 2025 in the Proceedings of the National Academy of Sciences. The authors include Zhe Shen, Bo Feng, Wei Ling Lim, Timothy Woo, Yanlin Liu, Silvia Vicenzi, Jingyi Wang, Brian K. Kwon, and Yimin Zou. Funding was provided by National Institute of Neurological Disorders and Stroke (grants R37 NS047484 and RO1 NS105961).

Source: University of California, San Diego

The post Gene Identified That Blocks Healing after Spinal Cord Injury appeared first on Spinal Cord Injury Information Pages.