South Korea’s Institute for Basic Science said it has identified what it called a root mechanism of brain damage in stroke and outlined a potential treatment approach, showing that blocking a “hydrogen peroxide–collagen production pathway” could suppress neuronal death.
The research team led by IBS Center Director Lee Changjoon, working with Eulji University, said on April 28 that it found a mechanism in which rising hydrogen peroxide during stroke activates astrocytes, and type I collagen produced in the process triggers the death of nerve cells.
Astrocytes typically help protect the brain and, during stroke, are known to form a glial barrier around damaged tissue to limit the spread of lesions. The team said it confirmed that this barrier can instead contribute to neuronal death, challenging the prevailing view.
Based on the mechanism, the researchers developed a drug candidate, KDS12025, designed to both remove hydrogen peroxide and inhibit collagen production. In a mouse stroke model, the team said, the drug sharply reduced glial barrier formation and neuronal death, and impaired motor function returned to normal levels within a week. The team also reported effects even when the drug was given two days after onset, suggesting the possibility of extending the “golden time” window often cited as a limitation in stroke treatment.
Similar results were reported in a primate model. Three days after KDS12025 was administered, lesion size decreased, and within a week, function returned in a hand that had been paralyzed, the researchers said. In a fruit-grasping test, the treated group succeeded in all 10 attempts, while the untreated group struggled because of motor impairment. The team said the primate findings support the potential for clinical application because of primates’ biological similarity to humans.
Lee Boyoung, an IBS research fellow, said the team identified at the molecular level a collagen-synthesis mechanism in astrocytes driven by reactive oxygen species. “It will provide an important clue not only for stroke but also for research on degenerative brain diseases such as dementia and Parkinson’s disease,” Lee said. Yoo Seungjun, a professor at Eulji University, said that demonstrating efficacy in a primate model could help speed the transition to clinical stages.
Lee Changjoon said the team succeeded in identifying a root cause and proposing a treatment strategy through a “one-stop research system” integrating basic research, drug development and preclinical work.
The findings were published online April 28 in the international journal Cell Metabolism.
* This article has been translated by AI.
Copyright ⓒ Aju Press All rights reserved.