In just four weeks, with this new treatment, the mice paralyzed due to spinal cord injuries was able to walk again.

In mice, a novel injectable treatment reversed paralysis and repaired tissue after severe spinal cord injuries. The findings are so promising that researchers from Northwestern University in Chicago (USA) will petition the US Food and Drug Administration (FDA) to start the approval process of this new therapy for use in patients.

They gave paralyzed mice a single injection to the tissues around their spinal cords. After just four weeks, the animals regained the ability to walk.

The findings were published in the journal Science.

The treatment is based on a polymer network formed by a mixture of chemicals that promotes axon regrowth, angiogenesis, and neuronal cell survival.

The therapy, according to the researchers, repairs the severely injured spinal cord in five key areas by sending bioactive signals to induce cells to repair and regenerate: it regenerates severed extensions of neurons, called axons; reduces scar tissue, which can create a physical barrier to regeneration and repair; promotes the formation of myelin, the insulating layer of axons that is important for efficiently transmitting electrical signals; and increases the formation of functional neurons.

Furthermore, after finishing its job, the materials biodegrade into nutrients for the cells in just 12 weeks and then entirely disappear from the body without causing any visible negative effects, according to the researchers.

“Our research aims to find a therapy that can prevent individuals from becoming paralyzed after major trauma or disease,” says 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.”

Only about 3% of individuals who have suffered a total injury ever regain basic bodily functions. And, following the first injury, almost 30% of patients are re-hospitalized at least once during the year, spending millions of dollars in average lifetime health care expenses per patient. Persons with spinal cord injuries have a lower life expectancy than people without them, and it hasn’t changed much since the 1980s.

“Currently, there are no therapeutics that trigger spinal cord regeneration,” acknowledges Stupp.

“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 key to Stupp’s new breakthrough therapy is fine-tuning molecular motion so that they can locate and appropriately engage continually moving cellular receptors.

When injected as a liquid, the treatment forms a complex network of nanofibers that closely resembles the extracellular matrix of the spinal cord.

The synthetic materials are able to communicate with cells by matching the matrix’s structure, simulating the mobility of biological components, and adding signals for receptors.

“Receptors in neurons and other cells constantly move around,” says the researcher. “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 nanofibers. 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.”

In paralyzed mice, Stupp and his colleagues discovered that fine-tuning the molecules’ mobility inside the nanofiber network to make them more responsive resulted in increased therapeutic efficacy. In vitro experiments with human cells revealed that formulations of their medication with higher molecular mobility functioned better, indicating increased bioactivity and cellular signaling.

“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. If the molecules are sluggish and not as ‘social,’ they may never come into contact with the cells.”

The moving molecules activate two cascading signals after attaching to the receptors, both of which are crucial for spinal cord healing. The long tails of neurons in the spinal cord, known as axons, renew in response to one signal. Axons transmit signals between the brain and the rest of the body in the same way that electrical cables do. Axon severance or damage can result in a lack of sensation in the body, as well as paralysis. Axon repair, on the other hand, improves communication between the brain and the body.

The second signal promotes the rebuilding of damaged blood arteries that feed neurons and essential cells for tissue repair, which helps neurons survive after injury. Glial scarring, which functions as a physical barrier that stops the spinal cord from repairing, is also reduced by the therapy, which causes myelin to regenerate around axons and reduces glial scarring.

“The signals used in the study mimic the natural proteins that are needed to induce the desired biological responses. However, proteins have extremely short half-lives and are expensive to produce,” says Zaida Álvarez, the study’s first author and former research assistant professor in Stupp’s laboratory. “Our synthetic signals are short, modified peptides that — when bonded together by the thousands — will survive for weeks to deliver bioactivity. The end result is a therapy that is less expensive to produce and lasts much longer.”

While Stupp believes the underlying discovery — that “supramolecular motion” is a key factor in bioactivity — can be applied to other therapies and targets, the new therapy could be used to prevent paralysis after major trauma (automobile accidents, falls, sports accidents, and gunshot wounds) as well as diseases.

“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.”

“Beyond that, our fundamental discovery about controlling the motion of molecular assemblies to enhance cell signaling could be applied universally across biomedical targets.”

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