Friday, November 12, 2021

Paralysed mice walk again after a single injection

The therapy, which the researchers hope to trial in humans, harnesses ‘dancing molecules’ to communicate with the body’s cells.

A new therapy, developed by researchers in the USA, has successfully reversed paralysis and repaired severe spinal cord injuries in mice. The animals regained the ability to walk only four weeks after a single injection of the treatment.

“Our research aims to find a therapy that can prevent individuals from becoming paralysed after major trauma or disease,” said Prof Samuel I Stupp of Northwestern University, 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.”

When the therapy is injected, the liquid immediately forms a network of nanofibres matching the structure around the spinal cord. The difficulty then is in communicating with the body’s cells.

“Receptors in neurons and other cells constantly move around,” said Stupp. So, as well as mimicking the structure of tissue around the spinal cord, the therapy is finely tuned to match the motion of the cellular receptors. This means that the molecules of the therapy are likely to come into contact with the moving receptors more often.

“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 nanofibres,” he 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.”

Then, once the molecules have connected with the receptors, they send two signals which kickstart the repair process. One talks to the axons, the ‘electrical cables’ that send signals to the brain, prompting them to regenerate. The other signal prompts cells to multiply, which can lead to blood vessels regrowing. As a result, the tissue will have a supply of blood, which is critical for repair. It is hoped that this second signal could help neurons to survive after injury.

A section of damaged spinal cord treated with the therapy. The regrown blood vessels are shown in red © Samuel I. Stupp Laboratory/Northwestern University

Other effects of the treatment include scar tissue being reduced and myelin, the insulation that surrounds axons, being reformed. Within 12 weeks of the injection, the materials in the therapy biodegrade into nutrients which are absorbed by cells. The therapy then completely disappears from the body with no reported side effects.

The researchers hope to begin human trials as soon as possible. “We are going straight to the FDA [the United States Food and Drug Administration] to start the process of getting this new therapy approved for use in human patients, who currently have very few treatment options,” said Stupp.

They also believe that this process of fine-tuning molecules to the motion of cells and receptors can be applied to treating other conditions.

“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 [motor neuron disease], Parkinson’s disease and Alzheimer’s disease,” Stupp said.

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