Temple University: Spinal Cord Injury and Optic Nerve Damage Repaired With Growth-Regulating Molecule

Researchers at Temple University have made a discovery that raises hope of restored functions for people with spinal cord injuries and other related issues.

Neuron

Neuron

In a study published in Molecular Therapy, researchers said they were able to regenerate neurons in mice that had spinal cord injury and optic nerve damage. They succeeded in restoring lost functions in the animals with the aid of a molecule called Lin28.

Several thousands of people suffer permanent losses of motor function and sensation due to spinal cord injury and similar conditions every year. These are results of severe damage or separation of axons.

Humans can regenerate most of the tissues in their bodies when damaged. Axons, however, fall among key body components that they are unable to redevelop when damaged.

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The new research by the Temple University scientists interestingly shows that Lin28 helps to mend axons. With the aid of the molecule, mice showed gains in sensation and recovery of motor function.

“Our findings show that Lin28 is a major regulator of axon regeneration and a promising therapeutic target for central nervous injuries,” said lead researcher Dr. Shuxin Li, MD, PhD.

The regenerative capacity of Lin28 was observed when it was expressed at levels higher than normal.

It was the first time scientists showed the potential of the molecule to help repair spinal cord injuries.

Regenerating axons

Axons are nerve fibers that project from neurons. They form networks that help to pass signals from the brain to different parts of the body. These long nerve fibers literally serve as communication cables.

The brain, for instance, depends on axons to be able to communicate with muscles. It is this interaction that enables movement in response to stimuli.

When axons are severed as a result of an injury or accident, sensation and motor function losses result. These changes last for the rest of a person’s life since the structures do not regenerate.

In the current research, scientists decided to explore the ability of Lin28 to regrow neurons. They developed an interest in this because of how it determines whether or not stem cells differentiate.

The study

The researchers developed a model involving over-expression of the focal molecule in certain tissues in mice. They put the animals in different groups containing those having a spinal cord injury or optic nerve damage after becoming adults.

Also, the team had a different group of mice with normal levels of Lin28 expression as well as spinal cord or optic nerve injuries. To examine tissue repair effects, the animals were injected with a viral vector that increases the expression of the molecule.

Expressions of Lin28 above normal levels promoted regeneration of axons in all the animals.

Lin28 injections led to axons extending up to 3 mm away from the point of severance or damage in animals with spinal cord injury. Axons grew again all along the whole length of the optic nerve tract.

The use of molecule injections proved to be the most effective means of restoring damaged axons.

When the researchers assessed the walking and sensory capabilities of the animals, they found that Lin28 therapy led to great improvements.

Future research

At the moment, there is no restorative treatment for people with injuries involving the spinal cord or optic nerve tracts, which link to the retina.

Li said the level of axon regeneration seen in the study could be highly significant in clinical terms. The professor of anatomy and cell biology revealed that one of his immediate plans was finding a means of making Lin28 helpful to human patients.

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He and colleagues need to create a carrier (or vector) for the molecule that would improve its expression when injected. They need to find a means of precisely targeting damaged axons with the treatment.

The researchers also planned to learn more about the Lin28 signaling pathway. Li expressed a suspicion that the molecule possibly uses more than one pathway to promote repair.

To support growth, the molecule seems to work with several others that could potentially be combined with it for more effective therapy.

References

https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(20)30191-X

 

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