Injectable 'dancing molecules' repair spinal cord injury, restore mobility in paralyzed mice

One popular idea for regenerating injured spinal cords is to implant artificial scaffolds bearing healing proteins near the injury site, but the idea has not panned out so far. Now, researchers at Northwestern University say they’ve found a way to make such a technique work, with two peptides that are altered so they amp up nerve regeneration.

The Northwestern team developed an injectable liquid containing the modified peptides, which form nanofibers similar to the spinal cord’s extracellular matrix. In mouse models of spinal cord injury, a single injection of the therapy promoted the regrowth of axons and restored walking ability, they reported in Science.

The key to the therapy is “dancing molecules,” explained lead author Samuel Stupp, Ph.D., a professor at Northwestern. His team mutated two peptide sequences: one that reduced scarring and the other that promoted the formation of blood vessels. That controlled the motion of the molecules in the nanofiber matrix in ways that promoted regeneration, Stupp said.

“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,” Stupp said in a statement.

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The moving molecules in the Northwestern study triggered signals critical to spinal cord repair, the Northwestern team observed. Promoting the regrowth of axons, which are the long tails at the end of neurons, improved communication between the brain and body. The therapy also reduced scarring, and the regrowth of blood vessels fed vital nutrients to cells needed to repair critical tissues.

After 12 weeks, the injected materials degraded into nutrients that continued to feed regenerative cells, the Northwestern team reported. There were no obvious side effects, they said.

This is one of several innovative approaches being investigated to prevent paralysis after spinal cord injury. Earlier this year, a University of Edinburgh team used the gene-editing technology CRISPR in zebrafish to pinpoint the gene TGFB1 as essential in promoting spinal cord repair.

UT Southwestern and Indiana University researchers genetically engineered cells to overproduce the healing protein Sox2, which improved mobility in mouse models of spinal cord injury. And a Temple University team found that boosting levels of the protein Lin28 in injured spinal cords prompted axon regrowth in mice.

The Northwestern researchers are planning to apply to the FDA to start human trials of their therapy, they said. They also believe their technique could be applied to other disorders marked by the loss of tissues in the central nervous system, including Parkinson’s and Alzheimer’s diseases, they added.