Clinical trial of the pan-caspase inhibitor, IDN-6556, in human liver preservation injury

E. S. Baskin-Bey, K. Washburn, S. Feng, T. Oltersdorf, D. Shapiro, Mi Ra Huyghe, L. Burgart, M. Garrity-Park, F. G.I. Van Vilsteren, L. K. Oliver, C. B. Rosen, G. J. Gores

Research output: Contribution to journalArticlepeer-review

135 Scopus citations


Cold ischemia/warm reperfusion (CI/WR) injury remains a problem in liver transplantation. The aim of the current study was to assess the utility of the pan-caspase inhibitor IDN-6556 on CI/WR injury during human liver transplantation. This report is a post hoc analysis of a Phase II, multi-center, randomized, placebo-controlled, double-blinded, parallel group study. Subjects were assigned to four treatment groups: Group 1 (Organ storage/flush: Placebo - Recipient: Placebo); Group 2 (Organ storage/flush: 15 μg/mL - Recipient: Placebo); Group 3 (Organ storage/flush: 5 μg/mL - Recipient: 0.5 mg/kg); and Group 4 (Organ storage/flush: 15 μg/mL - Recipient: 0.5 mg/kg). Liver cell apoptosis was assessed by serum concentrations of the apoptosis-associated CK18Asp396 ('M30') neo-epitope, TUNEL assay and caspase 3/7 immunohistochemistry. Liver injury was assessed by serum AST/ALT determinations. Serum markers of liver cell apoptosis were reduced in all groups receiving drug as compared to placebo. However, TUNEL, caspase 3/7 positive cells and serum AST/ALT levels were only consistently reduced in Group 2 (drug exposed to organ only). This reduction in serum transaminases was significant and observed across the study. In conclusion, IDN-6556 when administered in cold storage and flush solutions during liver transplantation offers local therapeutic protection against CI/WR-mediated apoptosis and injury. However, larger studies are required to confirm these observations.

Original languageEnglish (US)
Pages (from-to)218-225
Number of pages8
JournalAmerican Journal of Transplantation
Issue number1
StatePublished - Jan 2007


  • Apoptosis
  • Clinical trial
  • Cold ischemia/warm reperfusion injury
  • Neutrophil infiltration

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)


Dive into the research topics of 'Clinical trial of the pan-caspase inhibitor, IDN-6556, in human liver preservation injury'. Together they form a unique fingerprint.

Cite this