The 'Scar' That Caused Paralysis Turned into Nerve Cells... Hind Legs Move Again [Health LAB]

[Financial News] A new technology has been developed that converts scars formed after spinal cord injuries into nerve cells, helping restore movement lost to paralysis.
According to the Institute for Basic Science (IBS) on the 18th, the Cognition and Glioscience Group at the IBS Center for Memory and Glioscience, together with Professor Ha Yoon's research team at Yonsei University College of Medicine, devised a strategy to use glial scars as a resource for nerve regeneration. The teams developed TRANsCre-DIONE, a selective gene-expression technology.
According to the research team, spinal cord injury is a representative intractable disease in which nerve regeneration and functional recovery are severely limited once damage occurs. This is because reactive astrocytes proliferate excessively at the injury site and form a glial scar. The scar is known both as a defensive barrier that prevents further damage from spreading and as an obstacle that interferes with the regrowth of damaged neurons and the repair of neural circuits.
Using TRANsCre-DIONE, the team induced expression of Neurogenin-2 (Ng2)—a protein that acts as a switch prompting specific cells to differentiate into neurons—only in reactive astrocytes at spinal cord injury sites. The team then transdifferentiated the reactive astrocytes into functional neurons with motor neuron characteristics. The converted cells did more than merely take on the form of neurons. They fully performed neuronal functions by sending electrical signals and connecting with surrounding neural circuits to form synapses.
By directly converting only reactive astrocytes in the injured area into motor neurons, the team succeeded in restoring neural circuits.
Moreover, the team confirmed that Ng2, a master genetic switch, acted like a 'chameleon.' When injected into the cerebral striatum of mice, it converted the targeted cells into GABAergic neurons, which make up the largest proportion of cells in that region. When injected into the spinal cord, it converted them into motor neurons responsible for motor function. In other words, the researchers discovered a customized differentiation mechanism that can transform selected astrocytes into the neurons most needed in their surrounding environment.
When the technology was applied to a mouse striatal injury model, neurons were replaced with 62% efficiency. In particular, the team demonstrated a high targeting precision of 93.13% and the potential for cell conversion even in the striatum of crab-eating macaques, complex primates in which cell targeting is challenging. This confirmed the possibility of advancing the technology toward future clinical trials in humans. Furthermore, an experiment applying TRANsCre-DIONE to a mouse model of spinal cord injury recorded a world-leading neuronal conversion efficiency of 87%. The team successfully reconstructed neural circuits around the injury site and restored motor function in previously paralyzed hind legs.
The TRANsCre-DIONE system developed by the researchers induces nerve regeneration using only astrocytes already present in the body. It was designed to activate genes only in reactive astrocytes at the injury site without affecting normal cells. Therefore, unlike existing treatments such as stem-cell transplantation or the administration of external cells, it completely prevents serious adverse effects such as immune responses and tumor (cancer) formation at their source.
Changjoon Justin Lee, director of the research center and corresponding author, said, "TRANsCre-DIONE technology will be widely used to treat not only spinal cord injuries but also various neurological diseases, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and stroke," adding, "Just as astrocytes magically transform into neurons, I hope TRANsCre-DIONE will be put into practical use as soon as possible, bringing about the miraculous moment when patients with spinal cord injuries can stand again."
The findings were published online on September 11 in Experimental & Molecular Medicine, a sister journal of Nature.


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