The Integrated stress response (ISR) pathway is an evolutionarily conserved homeostatic program activated by specific pathological states including amino-acid deprivation, viral infection, iron deficiency or misfolded proteins within the Endoplasmic Reticulum (ER) leading to ER stress. Although apparently disparate, each of these stresses induces the phosphorylation of a translation initiation factor, eIF2, to attenuate protein translation while simultaneously triggering a specific transcriptional program allowing cells to cope with these pathological states.
Dysregulation of ISR signaling pathway leads to important pathological consequences such as neurodegenerative diseases, inflammation and cancers. Thus, pharmacological modulation of the ISR pathway represents a promising therapeutic strategy.
InFlectis BioScience is targeting the ISR pathway by modulating eIF2 phosphorylation level hence restoring proteostasis. InFlectisBioScience’s new generic approach will allow to treat a broad range of diseases with an immeasurable unmet clinical need.
The benefits of modulating eIF2 dephosphorylation with small chemical compounds were already demonstrated in multiple validated animal models of Charcot-Marie-Tooth, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Parkinson’s disease as well as in cancers.