Citation

  • Authors: Chauvier, D., Renolleau, S., Holifanjaniaina, S., Ankri, S., Bezault, M., Schwendimann, L., Rousset, C., Casimir, R., Hoebeke, J., Smirnova, M., Debret, G., Trichet, A. P., Carlsson, Y., Wang, X., Bernard, E., Hebert, M., Rauzier, J. M., Matecki, S., Lacampagne, A., Rustin, P., Mariani, J., Hagberg, H., Gressens, P., Charriaut-Marlangue, C., Jacotot, E.
  • Year: 2011
  • Journal: Cell Death Dis 2 e203
  • Applications: in vivo / siRNA / jetSI 10 mM

Abstract

Brain protection of the newborn remains a challenging priority and represents a totally unmet medical need. Pharmacological inhibition of caspases appears as a promising strategy for neuroprotection. In a translational perspective, we have developed a pentapeptide-based group II caspase inhibitor, TRP601/ORPHA133563, which reaches the brain, and inhibits caspases activation, mitochondrial release of cytochrome c, and apoptosis in vivo. Single administration of TRP601 protects newborn rodent brain against excitotoxicity, hypoxia-ischemia, and perinatal arterial stroke with a 6-h therapeutic time window, and has no adverse effects on physiological parameters. Safety pharmacology investigations, and toxicology studies in rodent and canine neonates, suggest that TRP601 is a lead compound for further drug development to treat ischemic brain damage in human newborns.

Pubmed