parogrelil (INDI 702) / Taisho - LARVOL DELTA

Drug repurposing screen identifies an HRI activating compound that promotes adaptive mitochondrial remodeling in MFN2-deficient cells. (PubMed, Proc Natl Acad Sci U S A) - "This screen identified the compounds parogrelil and MBX-2982 as potent and selective activators of the ISR through the OMA1-DELE1-HRI signaling axis. Moreover, we show that pharmacologic ISR activation afforded by parogrelil restores mitochondrial tubular morphology, promotes mitochondrial motility, rescues MERCs, and enhances mitochondrial respiration in MFN2-deficient cells. These results demonstrate the potential for pharmacologic ISR activation through the OMA1-DELE1-HRI signaling pathway as a potential strategy to mitigate mitochondrial dysfunction in CMT2A and other pathologies associated with MFN2 deficiency."

Journal • Genetic Disorders • Metabolic Disorders • Pain • KIF1B • MFN2

Drug Repurposing Screen Identifies an HRI Activating Compound that Promotes Adaptive Mitochondrial Remodeling in MFN2-deficient Cells. (PubMed, bioRxiv) - "This screen identified the compounds parogrelil and MBX-2982 as potent and selective activators of the ISR through the OMA1-DELE1-HRI signaling axis. Moreover, we show that pharmacologic ISR activation afforded by parogrelil restores mitochondrial tubular morphology, promotes mitochondrial motility, rescues MERCs, and enhances mitochondrial respiration in MFN2 -deficient cells. These results demonstrate the potential for pharmacologic HRI activation as a viable strategy to mitigate mitochondrial dysfunction in CMT2A and other pathologies associated with MFN2 deficiency."

Journal • Genetic Disorders • Metabolic Disorders • Pain • KIF1B • MFN2

Meta-analysis on Individual Patient Data from Randomized Controlled Trials of Fortasyn Connect in Early Alzheimer’s Disease (AAIC 2023) - "The total body of evidence available from RCTs suggests that Fortasyn Connect has a favorable effect on cognition and memory in early AD without any safety concerns, and consequently that this intervention is a viable option in the management of MCI due to AD (prodromal AD) and mild AD. Trial registration: clinicaltrialregister.nl (Souvenir I: NTR702; Souvenir II: NTR1975; LipiDiDiet: NTR1705)."

Retrospective data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders