A single injection of a newly developed drug has been shown to
reverse paralysis in mice with severe spinal cord injuries. By mimicking the extra-cellular matrix around the spine, the liquified drug promotes the regeneration of severed nerves and the repair of other vital tissues, allowing the rodents to regain the ability to walk within four weeks.
Describing this breakthrough in a new study in the journal
Science, researchers explain how they injected synthetic nanofibers into the damaged tissue of mice 24 hours after making a cut in their spinal cords. Consisting of an array of peptides, these nanofibers quickly assemble into a gel around the wound and begin communicating with cells in order to promote healing.
This is achieved thanks to the release of two vital signals, one of which activates a receptor called b1-integrin in order to promote the regrowth of
neuronal connecting arms, otherwise known as axons. The second signal, meanwhile, mimics a molecule called fibroblast growth factor 2, which helps neurons survive by supporting the development of other vital tissues such as blood vessels and myelin, which insulates nerve fibers.
Injured mice regained the ability to walk four weeks after receiving their injection. According to the study authors, the nanofibers then biodegrade into nutrients that can be taken up by cells, and are completely cleared from the body within 12 weeks.
However, the researchers state that the true genius of their work lies in a mutation that was incorporated into the peptide sequence, causing the molecules to become more mobile. Explaining the logic behind this approach, study author Samuel I. Stupp noted in a
statement that “receptors in neurons and other cells constantly move around,” and that “if the molecules are sluggish and not as ‘social,’ they may never come into contact with the cells.”
“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,” he explained.
“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.”
In their experiments, the researchers discovered that mice that were injected with these "dancing" molecules fared significantly better than those that were treated with peptides lacking this mutation. Stupp believes that this concept – which he calls “supramolecular motion” – may be the key to enhancing the bioactivity of molecular therapies, and could therefore be harnessed to boost the efficacy of a range of other treatments.
After euthanizing the healed mice and examining their repaired spinal cords, the researchers noted that axons had regenerated and that scar tissue – which can present a physical barrier to this regeneration – had diminished. In addition, myelin had formed around the repaired nerve fibers while blood vessels had also proliferated close to the wound site, allowing for vital nutrients to be delivered to the recovering neurons. As a consequence of all of these factors, motor neuron survival was greatly enhanced.
“Our research aims to find a therapy that can prevent individuals from becoming paralyzed after major trauma or disease,” said Stupp. “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.”
