Single injection can reverse severe spinal cord injuries

[Apr. 3, 2023: RS Shavit, The Brighter Side of News]

Researchers have developed a new injectable therapy that harnesses ‘dancing molecules’ to reverse paralysis and repair tissue after severe spinal cord injury. (CREDIT: Creative Commons)

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

Breakthrough therapy aims to prevent individuals from becoming paralyzed after major trauma or illness. Currently, there is no treatment that triggers spinal cord regeneration.

THE research will be published in the journal Science.

The research team administered a single injection into the tissues surrounding the spinal cord of paralyzed mice. Just four weeks later, the animals regained the ability to walk. By sending bioactive signals to trigger cell repair and regeneration, the breakthrough therapy dramatically improved severely injured spinal cords in five key ways.

The therapy biodegrades into nutrients for the cells within 12 weeks and then disappears completely from the body with no noticeable side effects.

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The therapy 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 treatment. “Our research aims to find a therapy that can prevent individuals from becoming paralyzed after major trauma or illness,” said Samuel I. Stupp of Northwestern, who led the study.

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. Life for these patients can be extraordinarily difficult. Less than 3% of people with a complete injury regain basic physical function. The life expectancy of people with spinal cord injuries is significantly lower than that of people without spinal cord injuries and has not improved since the 1980s.

The secret behind Stupp’s new therapeutic breakthrough is to tune the movement of molecules so they can find and properly engage ever-moving cellular receptors. Injected in liquid form, the therapy immediately gels into an intricate network of nanofibers that mimic the extracellular matrix of the spinal cord. By matching the structure of the matrix, mimicking the movement of biological molecules, and incorporating signals for receptors, synthetic materials can communicate with cells.

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)

Once connected to receptors, the moving molecules trigger two cascading signals, both essential for spinal cord repair. A signal prompts the long tails of neurons in the spinal cord, called axons, to regenerate. Cutting or damaging axons can lead to loss of sensation in the body or even paralysis.

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

A new injectable therapy forms nanofibers with two different bioactive signals (green and orange) that communicate with cells to initiate repair of the injured spinal cord. (CREDIT: Mark Seniw)

Stupp is a board professor of materials science and engineering, chemistry, medicine, and biomedical engineering at Northwestern, where he is founding director of the Simpson Querrey Institute for BioNanotechnology (SQI) and its affiliated research center, the Center for Regenerative Nanomedicine. He is appointed to the McCormick School of Engineering, the Weinberg College of Arts and Sciences, and the Feinberg School of Medicine.

Stupp and his team found that fine-tuning the movement of molecules within the nanofiber network to make them more agile resulted in greater therapeutic efficacy in paralyzed mice. They also confirmed that formulations of their therapy with enhanced molecular movement performed better in in vitro tests with human cells, indicating increased bioactivity and cell signaling.

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

The therapy biodegrades into nutrients for the cells within 12 weeks and then disappears completely from the body with no noticeable side effects. Researchers tested this therapy on mice and observed that it regenerated severed extensions of neurons, called axons, in the spinal cord of mice. This was a major breakthrough in the field of regenerative medicine, as there was previously no effective treatment to repair spinal cord nerve damage.

Shown here is a longitudinal section of the spinal cord treated with the most bioactive therapeutic scaffold, captured 12 weeks after injury. Regenerated blood vessels (red) in the lesion. Laminin is stained green and cells are stained blue. (CREDIT: Northwestern University)

Excited by these promising results, researchers began work on developing a version of the therapy for human use. They conducted extensive safety tests and clinical trials, which confirmed that the therapy was also safe and effective in humans.

As word of this revolutionary new therapy spread, patients with spinal cord injuries began to line up to receive the treatment. The first human trials were a resounding success, with many patients experiencing significant improvements in mobility and sensory function.

Over the next few years, the therapy became widely available and quickly became the standard of care for patients with spinal cord injuries. As a result, many people who were previously paralyzed or severely disabled have been able to regain their independence and lead more fulfilling lives.

By mutating the peptide sequence of amphiphilic monomers into non-bioactive domains, the researchers intensified the movements of molecules in the scaffold fibrils. (CREDIT: Science)

The success of this therapy has also inspired new research into other applications of regenerative medicine, and over time researchers have been able to develop similar treatments for a range of other conditions, including heart disease, heart failure liver and even some types of cancer.

Looking back, it is clear that the discovery of this therapy was a major turning point in the history of medicine and that it opened up new avenues for the treatment of previously incurable diseases. And while there’s still a lot of work to be done, the future looks bright for regenerative medicine and the millions of people it has the potential to help.

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

For more scientific news, see our New Innovations section on The bright side of the news.

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