A new analytical system has been developed to objectively identify animal models that best replicate the disease types of patients with intractable epilepsy. This advancement is expected to improve the accuracy of preclinical research and the success rate of new drug development for epilepsy treatments.
On August 6, Severance Hospital announced that research results, co-authored by clinical instructor Kim Jun-ho from the Department of Neurology at Yonsei University College of Medicine and researcher Lee Sang-bo from the Department of Biomedical Systems and Informatics, were published in the latest issue of the international journal Nature Communications. Professors Kim Sang-woo and Kim Won-joo served as co-corresponding authors.
The study was led by emerging physician-scientists trained through Yonsei University’s “Convergence Physician Scientist Training Program.”
Intractable epilepsy is a condition where seizures cannot be adequately controlled with medication alone. To develop new treatments, preclinical studies using animal models must be conducted before human trials can begin.
However, there has been a lack of objective criteria to determine which animal models best reflect the disease characteristics of specific patients. Researchers often relied on experience and convention when selecting animal models.
The research team conducted a large-scale transcriptome analysis by integrating 694 human brain tissue samples with 362 rodent brain tissue samples, including those from mice and rats. The transcriptome refers to the complete set of gene expressions in a cell and is used to understand the molecular characteristics of diseases.
They established a classification system called SIALAP, which categorizes animal models based on six criteria: species, method of epilepsy induction, route of drug administration, lateralization of epilepsy lesions, age, and disease phase.
The analysis revealed that a mouse model injected with kainate, an epilepsy-inducing substance, most closely mimicked the condition of patients with intractable epilepsy accompanied by hippocampal sclerosis. The hippocampus is the brain region responsible for memory and learning, and patients with hippocampal sclerosis exhibit damage to neurons in this area.
In contrast, a rat model induced with repeated electrical stimulation to trigger epilepsy best represented the condition of epilepsy patients without hippocampal sclerosis.
This is the first time that the molecular-level representation of different types of epilepsy patients by distinct animal models has been confirmed, according to the research team.
Kim Jun-ho, the clinical instructor, expressed hope that this research will contribute to more accurate preclinical studies and the development of effective treatments.
* This article has been translated by AI.
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