A study has found that brain diseases can occur even with mutation cells below 0.1%. The research results are expected to be applied and utilized in developing therapeutics that precisely target mutation cells.
KAIST announced on the 9th that Professor Jeongho Lee's research team at the Graduate School of Medical Science and Engineering demonstrated that an extremely small amount of mutated nerve cells can cause dysfunction of the entire brain, leading to epileptic seizures.
The research team established new criteria for diagnosing mutation genes in intractable epilepsy through animal models of pediatric intractable epilepsy caused by brain cell-specific mutations (brain somatic mosaicism) and studies of patient brain tissues, revealing that an extremely small amount of mutated nerve cells can be involved in causing various brain diseases.
The study was conducted to find answers to how the accumulation of specific gene mosaicism in a very small number of cells leads to brain disease occurrence that induces overall brain dysfunction.
The research team induced epilepsy-causing somatic mosaicism in the brain tissues of experimental mice in as few as several hundred to as many as tens of thousands of cells. They observed that when about 8,000 to 9,000 mutated nerve cells appeared, the experimental mice began to experience epileptic seizures and related pathologies.
Additionally, ultra-high depth amplicon sequencing was performed on brain tissues from patients with intractable epilepsy to accurately measure the mutation mosaicism ratio, observing epilepsy-causing somatic mosaicism as low as 0.07%.
This discovery can aid in the genetic precision diagnosis of intractable epilepsy, which does not respond to drug treatment and leads to surgery, and suggests that intractable neuropsychiatric disorders with unknown causes are closely related to minute micro-mutations occurring during brain development and differentiation processes.
The research team anticipates that this study will lay an important foundation for improving diagnostic methods for focal cortical dysplasia and discovering causes of brain diseases caused by somatic mosaicism. Focal cortical dysplasia is a disease in which abnormalities in nerve cells occur locally in the cerebral cortex during brain development and is known as the most important cause of pediatric intractable epilepsy that does not respond at all to existing anti-epileptic drugs.
The research outcomes will also be used for developing innovative RNA therapeutics that precisely target somatic mosaicism mutations in patients with intractable epilepsy through Sobagen Co., Ltd., a KAIST faculty startup company.
Meanwhile, this research was conducted with support from the Seok Kyung-bae Science Foundation, the National Research Foundation of Korea, and the Korea Health Industry Development Institute. The research results were also published in the world-renowned neurology journal Brain on the 25th of last month.
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