A joint research team of Severance Hospital and Chungnam National University has confirmed the possibility of treating people with vanishing white matter disease (VWMD) by identifying the pathological mechanism in an originally developed zebrafish model.

The researchers developed an animal model of VWMD using genetic analysis, zebrafish, and gene-editing technology called the CRISPR. 

Based on the model, the researchers have discovered that zebrafish that lacked a protein-coding gene, known as EIF2B3 (Eukaryotic Translation Initiation Factor 2B Subunit Gamma), showed a deficiency in producing neurological myelin to the control group that did not have such a problem. EIF2B3 is involved in the early stage of myelination creation and exerts influence on the occurrence and differentiation of neuroglia cells. 

According to the team, VWMD is a rare neurological disease difficult to find with no available treatment. It is a progressive disease caused by mutation of EIF2B3 that destroys white matter within the central nervous system.

The disease’s symptoms include ataxia, stiffness, hypotonia, and convulsions, leading to movement impairment. Most of the babies who develop the disease within a year of birth die in a few years. Its exact pathogenesis has not been discovered, and there are no known therapies for the disease.

Myelin protects nerve cells in the brain, and a normal myelin sheath allows electrical impulses to transmit quickly and efficiently along with the nerve cells, improving the ability to store memories, think logically, and have abstract thoughts.

 “Although the development of a therapeutic agent is urgently needed, it has been difficult to pick a candidate substance for clinical trials due to the lack of understanding of the pathologic mechanism,” the research team said. “The joint study has revealed the pathologic mechanism of VWMD and presented a therapeutic target, providing a successful intermediary model for developing  its.”

Professors Kim Se-hee and Kang Hoon-chul of the Pediatric Neurology Department of Severance Hospital and Professor Kim Cheol-hee of the Department of Biology at Chungnam National University led the study and published the study results in Human Molecular Genetics.

The research was conducted with the support of the Ministry of Science and ICT and the National Research Foundation of Korea for promoting biomedical technology development.