Science

Mechanism of Action


Resalis is applying the cutting-edge LNA (locked nucleic acid) technology to inhibit miR-22 activity and restore a healthy homeostat in livers affected by metabolic disorders. miR-22 is a key player in the regulation of lipid metabolism and its levels are correlated with several metabolic disfunction including NAFLD (MAFLD) and obesity. Pharmacological inhibition of miR-22 proved able to protect mice from MAFLD and obesity, and to revert hepatic steatosis and fat accumulation in obese animals, paving the way for the development of anti-MAFLD therapy for humans.

Metabolic syndromes are very complex diseases regulated via multiple pathways, including several miR-22 target genes. Mechanistically, miR-22 orchestrates multiple pro-lipogenic programs modulating both direct and indirect targets. Inhibition of miR-22 via ASO LNA helps restoring regulation of lipid biosynthesis and promotes metabolic rewiring towards higher energy expenditure and browning of white adipose tissue, showing in parallel also a positive effect on prevention of fibrosis and inflammation.

Pipeline


Publications


Thibonnier, M., Esau, C., Ghosh, S., Wargent, E., & Stocker, C. (2020). Metabolic and energetic benefits of microRNA-22 inhibition. BMJ Open Diabetes Research and Care, 8(1), e001478.

Diniz, G. P., Huang, Z. P., Liu, J., Chen, J., Ding, J., Fonseca, R. I., … & Wang, D. Z. (2017). Loss of microRNA-22 prevents high-fat diet induced dyslipidemia and increases energy expenditure without affecting cardiac hypertrophy. Clinical Science, 131(24), 2885-2900.

Lou, P., Bi, X., Tian, Y., Li, G., Kang, Q., Lv, C., … & Yu, Z. (2021). MiR-22 modulates brown adipocyte thermogenesis by synergistically activating the glycolytic and mTORC1 signaling pathways. Theranostics, 11(8), 3607.

Kaur, K., Vig, S., Srivastava, R., Mishra, A., Singh, V. P., Srivastava, A. K., & Datta, M. (2015). Elevated hepatic miR-22-3p expression impairs gluconeogenesis by silencing the Wnt-responsive transcription factor Tcf7. Diabetes, 64(11), 3659-3669.

Yang, Z., Qin, W., Huo, J., Zhuo, Q., Wang, J., & Wang, L. (2021). MiR‐22 modulates the expression of lipogenesis‐related genes and promotes hepatic steatosis in vitro. FEBS Open Bio, 11(1), 322-332.

Hu, Y., Liu, H. X., Jena, P. K., Sheng, L., Ali, M. R., & Wan, Y. J. Y. (2020). miR-22 inhibition reduces hepatic steatosis via FGF21 and FGFR1 induction. JHep Reports, 2(2), 100093.