Application of ISR inhibitor ISRIB in preparation of medicine for treating Wolfram syndrome

• Main Authors: ZHANG ZHENNING, HU RUI, CHEN XIANGYI, LI WEIDA
• Format: Patent
• Language: Chinese; English
• Published: 07.06.2024
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

The invention discloses an application of an ISR inhibitor ISRIB in preparation of a medicine for treating Wolfram syndrome. In a Wolfram syndrome in-vitro model with a WFS1 gene knocked out and a mouse model with a WFS1 gene conditionally knocked out, it is verified that ISRIB can relieve pancreatic beta cell function failure; iSRIB is added into neuron cells with WFS1 gene deletion, and it is found that the neuron apoptosis level really caused by WFS1 is recovered. The invention proves that ISRIB enhances the survival ability of pancreatic beta cells and neurons by inhibiting ISR, relieves the function failure of the pancreatic beta cells, and can be subsequently used for treating Wolfram syndrome diabetes mellitus and neuronal degenerative change. 本发明公开了ISR抑制剂ISRIB在制备治疗Wolfram综合征的药物中的应用。本发明利用WFS1基因敲除的Wolfram综合征体外模型和WFS1基因条件性敲除的小鼠模型中，验证ISRIB可缓解胰岛β细胞功能衰竭；WFS1基因缺失的神经元细胞中，加入ISRIB，发现WFS1确实导致的神经元凋亡水平被恢复。本发明证实了ISRIB通过抑制ISR增强胰岛β细胞与神经元的存活能力，缓解胰岛β细胞功能衰竭，后续可用于治疗Wolfram综合征糖尿病变与神经元退行性病变。