Regenerative Medicine Breakthrough: “Dancing Molecules” Successfully Repair Severe Spinal Cord Injuries
Longitudinal spinal cord section treated with the most bioactive therapeutic scaffold. Regenerated axons (red) regrew within the lesion. Credit: Samuel I. Stupp Laboratory/Northwestern University
After single injection, paralyzed animals regained ability to walk within four weeks.
Northwestern University researchers have developed a new injectable therapy that harnesses “dancing molecules” to reverse paralysis and repair tissue after severe spinal cord injuries.
In a new study, researchers administered a single injection to tissues surrounding the spinal cords of paralyzed mice. Just four weeks later, the animals regained the ability to walk.
The research will be published in the November 12, 2021, issue of the journal Science.
Longitudinal spinal cord section treated with the most bioactive therapeutic scaffold, captured 12 weeks after injury. Blood vessels (red) regenerated within the lesion. Laminin is stained in green and cells are stained in blue. Credit: Samuel I. Stupp Laboratory/Northwestern University
By sending bioactive signals to trigger cells to repair and regenerate, the breakthrough therapy dramatically improved severely injured spinal cords in five key ways: (1) The severed extensions of neurons, called axons, regenerated; (2) scar tissue, which can create a physical barrier to regeneration and repair, significantly diminished; (3) myelin, the insulating layer of axons that is important in transmitting electrical signals efficiently, reformed around cells; (4) functional blood vessels formed to deliver nutrients to cells at the injury site; and (5) more motor neurons survived.
After the therapy performs 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 controlled the collective motion of molecules through changes in chemical structure to increase a therapeutic’s efficacy.
A simple animation shows how a single injection restores connections in the nervous system below the site of a severe spinal cord injury. Credit: Samuel I. Stupp Laboratory/Mark Seniw/Northwestern University
“Our research aims to find a therapy that can prevent individuals from becoming paralyzed after major trauma or disease,” said Northwestern’s 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.”
Stupp is Board of Trustees 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 has appointments in the McCormick School of Engineering, Weinberg College of Arts and Sciences, and Feinberg School of Medicine.
A paralyzed mouse (left) drags its hind legs, compared to a paralyzed mouse that has regained its ability to move its legs after receiving Northwestern’s injectable therapy. Credit: Samuel I. Stupp Laboratory/Northwestern University
Life expectancy has not improved since the 1980s
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 complete injury ever recover basic physical functions. And approximately 30% are re-hospitalized at least once during any given year after the initial injury, costing millions of dollars in average lifetime health care costs per patient. Life expectancy for people with spinal cord injuries is significantly lower than people without spinal cord injuries and has not improved since the 1980s.
“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.”
— Samuel I. Stupp, materials scientist
“Currently, there are no therapeutics that trigger spinal cord regeneration,” said Stupp, an expert in regenerative medicine. “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.”
‘Dancing molecules’ hit moving targets
The secret behind Stupp’s new breakthrough therapeutic is tuning the motion of molecules, so they can find and properly engage constantly moving cellular receptors. Injected as a liquid, the therapy immediately gels into a complex network of nanofibers that mimic the extracellular matrix of the spinal cord. By matching the matrix’s structure, mimicking the motion of biological molecules and incorporating signals for receptors, the synthetic materials are able to communicate with cells.
“Receptors in neurons and other cells constantly move around,” Stupp said. “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.”
from scitechdaily 16/11/2021
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