Accessible Requires Authentication Published by De Gruyter June 18, 2011

PETIR-001, a dual inhibitor of dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN), ameliorates experimental autoimmune encephalomyelitis in SJL/J mice

Dirk Reinhold, Ute Bank, Dominik Entz, Alexander Goihl, Diana Stoye, Sabine Wrenger, Stefan Brocke, Anja Thielitz, Sofia Stefin, Karsten Nordhoff, Anke Heimburg, Michael Täger and Siegfried Ansorge
From the journal


Cellular dipeptidyl peptidase IV (DP IV, CD26) and amino-peptidase N (APN, CD13) play regulatory roles in T cell activation and represent potential targets for treatment of inflammatory disorders. We have developed a novel therapeutic strategy, ‘peptidase-targeted Immunoregulation’ (PETIR™), which simultaneously targets both cellular DP IV and APN via selective binding sites different from the active sites with a single inhibitor. To prove the therapeutic concept of PETIR™ in autoimmunity of the central nervous system (CNS), we evaluated the effect of a single substance, PETIR-001, in an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. Administration of PETIR-001 significantly delayed and decreased clinical signs of active EAE, when given in a therapeutic manner intraperitoneally from day 15 to day 24 after induction of EAE. Both the acute phase and the first relapse of EAE were markedly inhibited. Importantly, a similar therapeutic benefit was obtained after oral administration of PETIR-001 from day 12 to day 21 after disease induction. Our results demonstrate that PETIR-001 exhibits a therapeutic effect on EAE in SJL/J mice. Thus, PETIR™ represents a novel and efficient therapeutic approach for immunotherapy of CNS inflammation.

Corresponding author

Received: 2010-6-24
Accepted: 2010-11-2
Published Online: 2011-06-18
Published in Print: 2011-03-01

©2011 by Walter de Gruyter Berlin New York