A single injection eliminates paralysis after severe spinal cord injury.

Researchers have developed a new injectable therapy that uses “dancing molecules” to reverse paralysis and repair tissue after severe spinal cord injuries. (CREDIT: Creative Commons)

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

In the new study, the researchers injected a single injection into the tissues surrounding the spinal cords of paralyzed mice. In just four weeks, the animals regained the ability to walk.

The study will be published in the journal Science.

By sending bioactive signals to cause cells to repair and regenerate, the revolutionary therapy significantly improved the severely damaged spinal cord in five key ways: (1) torn neuronal extensions called axons were regenerated; (2) scar tissue, which can provide a physical barrier to regeneration and repair, has been greatly reduced; (3) myelin, the insulating layer of axons that is important for the efficient transmission of electrical signals, regenerates around cells; (4) functional blood vessels formed to deliver nutrients to cells at the site of injury; and (5) more motor neurons survived.

After the therapy has performed 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 have controlled the collective movement of molecules through changes in chemical structure to increase the effectiveness of a therapeutic agent.

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“Our study aims to find a therapy that can prevent paralysis in people after a major injury or illness,” said Northwestern’s Samuel I. Stupp, who led the study. “For decades, this has remained a major problem for scientists because our body’s central nervous system, which includes the brain and spinal cord, does not have any significant ability to recover from injury or from the onset of degenerative disease. We are going straight to the FDA to begin the process of approving this new therapy for use in people who currently have very few treatment options.”

Stupp is a Board of Trustees Professor in Materials Science and Engineering, Chemistry, Medicine, and Biomedical Engineering at Northwestern University, where he is the founding director of the Simpson Querry Bionanotechnology Institute (SQI) and its sister research facility, the Center for Regenerative Nanomedicine. He works at the McCormick School of Engineering, the Weinberg College of Arts and Sciences, and the Feinberg School of Medicine.

Life expectancy has not increased since the 1980s

According to the National Spinal Cord Injury Statistical Center, about 300,000 people are currently living with spinal cord injuries in the United States. The life of such patients can be extremely difficult. Fewer than 3% of people with a complete injury ever regain basic physical function. And roughly 30% are rehospitalized at least once in any year after the initial injury, costing millions of dollars in average lifetime healthcare costs per patient. The life expectancy of people with spinal cord injuries is significantly lower than that of people without spinal cord injuries and has not increased since the 1980s.

This GIF shows a side-by-side comparison of an untreated mouse next to a mouse treated with Northwestern’s injectable therapeutic. (CREDIT: Northwestern University)

“Currently, there are no therapeutics that trigger the regeneration of the spinal cord,” said Stupp, an expert in regenerative medicine. “I wanted to change the outcome of spinal cord injury and address this issue given the huge impact it can have on patients’ lives. In addition, the new science of spinal cord injury may influence treatment strategies for neurodegenerative diseases and stroke.”

“Dancing molecules” hit moving targets

The secret behind Stuppa’s breakthrough new therapeutic lies in fine-tuning the movement of the molecules so they can find and properly engage constantly moving cell receptors. Administered as a liquid, the therapy immediately gels into a complex network of nanofibers that mimic the extracellular matrix of the spinal cord. By conforming to the structure of the matrix, imitating the movement of biological molecules, and including signals for receptors, synthetic materials can interact with cells.

The new injection therapy forms nanofibers with two different biologically active signals (green and orange) that interact with cells to initiate repair of the damaged spinal cord. (CREDIT: Mark Seniv)

“Receptors in neurons and other cells are constantly moving,” Stupp said. “A key innovation in our research that has never been seen before is to control the collective movement of over 100,000 molecules within our nanofibers. By making molecules move, dance, or even temporarily jump out of these structures, known as supramolecular polymers, they can bind to receptors more efficiently.”

Stupp and his team found that fine-tuning the movement of molecules in the nanofiber network to make them more mobile results in greater therapeutic efficacy in paralyzed mice. They also confirmed that their enhanced molecular motion therapy formulations performed better during in vitro testing with human cells, indicating increased biological activity and cellular signaling.

“Given that the cells themselves and their receptors are in constant motion, you can imagine that molecules moving faster will collide with these receptors more often,” Stupp said. “If the molecules are sluggish and not so ‘social’, they may never make contact with cells.”

One injection, two signals

Once connected to the receptors, the moving molecules trigger two cascade signals, both of which are critical for spinal cord repair. One signal causes the long tails of neurons in the spinal cord, called axons, to regenerate.

Like electrical cables, axons send signals between the brain and the rest of the body. Rupture or damage to axons can lead to loss of sensation in the body or even paralysis. On the other hand, axon repair increases communication between the body and the brain.

The second signal helps neurons survive injury because it causes other cell types to proliferate, promoting the regrowth of lost blood vessels that nourish neurons and critical cells for tissue repair. The therapy also causes the restoration of myelin around axons and reduces glial scarring, which acts as a physical barrier that prevents the spinal cord from healing.

“The signals used in the study mimic natural proteins needed to induce desired biological responses. However, proteins have an extremely short half-life and are expensive to manufacture,” says Zaida Alvarez, first author of the study and a former assistant professor at Stuppa’s lab. “Our synthetic signals are short, modified peptides that, when linked together by the thousands, retain their biological activity for several weeks. The end result is a therapy that is cheaper to produce and lasts much longer.”

Shown here is a longitudinal section of the spinal cord treated with the most bioactive therapeutic scaffold obtained 12 weeks after injury. Blood vessels (red) regenerated at the lesion. Laminin stains green and cells stain blue. (CREDIT: Northwestern University)

Universal Application

While the new therapy could be used to prevent paralysis from major trauma (car crashes, falls, sports injuries, and gunshot wounds) as well as from disease, Stupp believes the underlying finding is that “supramolecular motion” is key. biological activity – can be applied to other treatments and targets.

“The central nervous system tissue that we have successfully regenerated in spinal cord injury is similar to brain tissue affected by stroke and neurodegenerative diseases such as ALS, Parkinson’s disease and Alzheimer’s disease,” Stupp said. “In addition, our fundamental discovery about controlling the movement of molecular assemblies to enhance cellular signaling can be universally applied to biomedical targets.”

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Note: Materials provided above by Northwestern University. Content can be edited for style and length.

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