Longitudinal spinal cord slices treated with the most biologically active therapeutic scaffold. The regenerated axon (red) grows back in the lesion. Image source: Samuel I. Stupp Lab/Northwestern University

After a single injection, the paralyzed animals regained the ability to walk within 4 weeks.

Researchers at Northwestern University have developed a new injectable therapy that uses "dancing molecules" to reverse paralysis and repair tissue after severe spinal cord injury.

In a new study, researchers injected an injection into the tissue surrounding the spinal cord of paralyzed mice. After only four weeks, these animals regained their ability to walk.

The research will be published in the journal Science on November 12, 2021.

Longitudinal spinal cord slices treated with the most biologically active therapeutic scaffold, captured 12 weeks after injury. The blood vessels (red) regenerate in the lesion. Laminin is stained green, and cells are stained blue. Image source: Samuel I. Stupp Lab/Northwestern University

By sending biologically active signals to trigger cell repair and regeneration, the breakthrough therapy significantly improved the severely injured spinal cord in five key areas: (1) the regeneration of the severed extension of the neuron (called axon); (2) The scar tissue that causes physical obstacles to regeneration and repair is significantly reduced; (3) Myelin sheath, the insulating layer of axons, is important for effective transmission of electrical signals, and reorganizes around cells; (4) Forms functional blood vessels, which are the damage site Cells deliver nutrients; (5) More motor neurons survive.

After the treatment is completed, the material will biodegrade into cellular nutrients within 12 weeks, and then disappear completely from the body without significant side effects. This is the first study in which researchers control the collective movement of molecules through changes in chemical structure to improve therapeutic effects.

A simple animation shows how a single injection restores the connection to the nervous system below the severely injured spinal cord. Image source: Samuel I. Stupp Laboratory/Mark Seniw/Northwestern University

"Our research aims to find a treatment that can prevent individuals from becoming paralyzed after suffering a major trauma or illness," said the leader of the study, Samuel I. Stupp of Northwestern University. "For decades, this has been a major challenge for scientists, because our body's central nervous system, including the brain and spinal cord, does not have any significant self-repair ability after injury or degenerative disease. We will directly The FDA is seeking to approve this new therapy for human patients who currently have very few treatment options."

Stupp is the board professor of materials science and engineering, chemistry, medicine, and biomedical engineering at Northwestern University. He is the founding director of the Simpson Quay Institute for Bio-Nanotechnology (SQI) and its affiliated research center, the Center for Regenerative Nanomedicine. He has held positions at the McCormick School of Engineering, Weinberg School of Arts and Sciences, and Feinberg School of Medicine.

A paralyzed mouse (left) drags its hind legs, and a paralyzed mouse has regained the ability to move its legs after receiving Northwestern injection therapy. Image source: Samuel I. Stupp Lab/Northwestern University

According to the National Spinal Cord Injury Statistics Center, nearly 300,000 people in the United States currently suffer from spinal cord injury. The lives of these patients can be extremely difficult. Less than 3% of people who are completely injured are able to recover basic body functions. Approximately 30% of people are hospitalized at least once in any year after their first injury, and the average lifetime medical care cost per patient is as high as millions of dollars. The life expectancy of patients with spinal cord injury is significantly lower than that of patients without spinal cord injury and has not improved since the 1980s.

"Given that spinal cord injury can have a huge impact on patients' lives, I want to change the outcome of spinal cord injury and solve this problem." — Samuel I. Stupp, materials scientist

"Currently, there is no therapy to trigger spinal cord regeneration," said Stupp, an expert in regenerative medicine. "Given that spinal cord injury can have a huge impact on patients' lives, I want to change the outcome of spinal cord injury and solve this problem. In addition, new science to address spinal cord injury may have an impact on strategies for neurodegenerative diseases and stroke."

The secret behind Stupp's new breakthrough therapy is to adjust the movement of molecules so they can find and properly engage the constantly moving cell receptors. After injection in liquid form, the therapy immediately condenses into a complex network of nanofibers that mimics the extracellular matrix of the spinal cord. By matching the structure of the matrix, simulating the movement of biomolecules, and combining receptor signals, synthetic materials can communicate with cells.

"The receptors in neurons and other cells are constantly moving," Stupp said. "The key innovation of our research is to control the collective motion of more than 100,000 molecules in our nanofibers, which has never been done before. By allowing molecules to move,'dance' or even temporarily jump out of these structures, that is, supramolecular polymers, they Can connect with receptors more effectively."

Due to the rapid movement of molecules, nanofibers containing molecules with two different biological activity signals (green and orange) bind to cell receptors (yellow and blue) more effectively. Image source: Samuel I. Stupp Laboratory/Mark Seniw/Northwestern University

Stupp and his team found that fine-tuning the movement of molecules within the nanofiber network makes them more flexible, which will have a greater therapeutic effect on paralyzed mice. They also confirmed that in in vitro tests on human cells, therapeutic formulations that enhance molecular movement performed better, indicating increased biological activity and cell signaling.

"Given the cells themselves and their receptors are constantly in motion, you can imagine that molecules that move faster will encounter these receptors more frequently," Stupp said. "If the molecules are sluggish and not'social', they may never come into contact with the cell."

Once connected to the receptor, the moving molecule triggers two cascades of signals that are essential for spinal cord repair. A signal causes the long tails (called axons) of neurons in the spinal cord to regenerate. Similar to cables, axons send signals between the brain and other parts of the body. Severing or damaging the axons can cause the body to lose consciousness and even become paralyzed. On the other hand, repairing axons can increase communication between the body and the brain.

The second signal helps neurons survive injury because it causes other types of cells to proliferate and promotes the regeneration of lost blood vessels, which provide nutrients for neurons and cells that are critical for tissue repair. The therapy also induces the remodeling of myelin sheath around the axons and reduces the formation of glial scars, which act as a physical barrier that prevents the spinal cord from healing.

A new injectable therapy forms nanofibers with two different biologically active signals (green and orange) that communicate with cells to initiate repair of the damaged spinal cord. Image source: Illustration by Mark Seniw

"The signal used in the study mimics the natural protein needed to induce the desired biological response. However, the protein has an extremely short half-life and is expensive to produce," said Zaida Álvarez, the first author of the study. "Our synthetic signal is that short modified peptides-when thousands of peptides are combined-will survive for several weeks to provide biological activity. The end result is a therapy that is cheaper to produce and lasts longer. ."

Alvarez was a research assistant professor in the Stupp laboratory and is now a visiting scholar at SQI and a researcher at the Catalan Institute of Bioengineering in Spain.

Although the new therapies can be used to prevent major traumas (car accidents, falls, sports accidents, and gunshot wounds) and paralysis after illness, Stupp believes that the underlying discovery-"supramolecular motion" is a key factor in biological activity-can be applied Other therapies and targets.

"The central nervous system tissue that we successfully regenerate in the injured spinal cord is similar to the tissue in the brain affected by stroke and neurodegenerative diseases such as ALS, Parkinson's disease, and Alzheimer's disease," Stupp said. "In addition, our basic findings about controlling the movement of molecular assembly to enhance cell signaling can be widely applied to biomedical goals."

Reference: "Bioactive scaffolds with enhanced supramolecular movement promote recovery from spinal cord injury" Authors: Z. Álvarez, AN Kolberg-Edelbrock, IR Sasselli, JA Ortega, R. Qiu, Z. Syrgiannis, PA Mirau, F. Chen, SM Chin, S. Weigand, E. Kiskinis and SI Stupp, November 11, 2021, Science. DOI: 10.1126/science.abh3602

Other Northwestern University study authors include Evangelos Kiskinis, assistant professor of neurology and neuroscience at Feinberg; Feng Chen, research technician; postdoctoral researchers Ivan Sasselli, Alberto Ortega, and Zois Syrgiannis; and graduate students Alexandra Kolberg-Edelbrock, Ruomeng Qiu, and Stacey Chin . Peter Mirau of the Air Force Research Laboratory and Steven Weigand of the Argonne National Laboratory are also co-authors.

The research titled "Bioactive scaffolds with enhanced supramolecular motion to promote recovery from spinal cord injury" was supported by Louis A. Simpson and Kimberly K. Querrey Center for Regenerative Nanomedicine of the Simpson Querrey Institute of Bio-Nanotechnology, Air Force Research Laboratory Support (winning) No. FA8650-15-2-5518), National Institute of Neurological Diseases and Stroke and National Institute of Aging (Award No. R01NS104219, R21NS107761 and R21NS107761-01A1), Les Turner ALS Foundation, New York Paralytic Stem Cell Foundation The American Veterans Research Foundation (award number PVA17RF0008), the National Science Foundation and the French Muscular Dystrophy Association.

I hope to be useful to people who are not paralyzed. People like me who suffer from degenerative disc disease and spine are falling apart. I also have obvious scar tissue. This sounds great!

What I need to know is whether this is effective for people with old injuries, such as 20 years old. Please answer. Thank you.

I want to know the same thing? ? ?

Can this also help MS patients?

Wow, I am a retired agent. He was shot in 1971 and injured the spinal cord of L1-2, but it was not severed. For the past 50 years, I have been using long-leg braces and crutches to improve mobility, and I continue to do so today. If volunteer patients are needed, I would be happy to be a volunteer. Any improvement will be a gift.

Does this help patients with Stiff Man Syndrome?

I am a speech pathologist working with elderly people, many of whom suffer from spinal cord problems for various reasons. This app has such a promise.

What about diseases like spina bifida? Can these people volunteer to participate in the experiment? How do they sign up for the trial?

That's great. It’s great to hear that spinal injuries may be treated soon. I want to know if the same type of treatment can be used on shrunken and crushed intervertebral discs because my father often has back pain.

I will see my mother walking again, or maybe only with the walker she deserves

I had a car accident and my rest time was my T12-L1 spinal cord injury. Paralyzed under the break. I live with constant neuralgia in my legs and feet. The pain level will never be lower than 6/u, and I often have pain at the 9/10 level. I went to the pain clinic, but there was no relief. Currently I take takong percocet 10mg and Lyrica 200mg 3 times a day. I usually have to go to the emergency room at least once a week to relieve this short-term pain. I am a 31 year old male and I really want some relief.

I suffered a retroperitoneal groin injury due to a blood clot in the PICC line, which severely damaged my left leg. I really want to be a volunteer test subject!

I am interested in knowing if it is a potential treatment for neuropathy!

Wow, this sounds like the repaired nanotechnology in the Voyager and the nanomachines in the Metal Gear series. This is god-level science.

I want to know if I couldn't get the doctor to do anything after a drunk driver almost killed me 21 years ago. To this day, my back is numb and my whole body is tingling. I need help. I was 39 years old.

If they take out part of the spine and replace it with rods and screws, will this work? A patient with MS who suffers from nerve damage and cannot use his limbs?

My wife broke her neck in a horse accident five years ago. She is numb to walk now. Her legs fell from her knees, and her hands were numb from elbows to fingers. She has severe neuralgia. Do you think it will help her?

My husband suffers from transverse myositis and has problems with his left leg being affected and dragged. Does this help him?

Can this be used for cauda equina syndrome? I have this and know that many other people do the same, all over the world. Reading this discovery, I really cried and even thought there was a silver lining! After this nightmare lasted for 15 years, it would be a blessing to get rid of the paralysis of the intestines and bladder area.

I was involved in a motorcycle accident. So far, I have performed 2 neck surgeries and 2 back surgeries. Due to nerve damage (foot drop), my left leg continued to have peripheral neuropathy. I am very interested in receiving injections to repair my nerves,

I will sign up for the test

I am willing to do anything to try this! I hope the FDA will give them the green light and let them enter clinical trials. This gives us great hope for spinal cord patients who are looking for some kind of answer.

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