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' (PETIRbeta), 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 PETIRbeta 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, PETIRbeta represents a novel and efficient therapeutic approach for immunotherapy of CNS inflammation.
        
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Reinhold D, Bank U, Entz D, Goihl A, Stoye D, Wrenger S, Brocke S, Thielitz A, Stefin S, Nordhoff K, Heimburg A, Tager M, Ansorge S (2011) PETIR-001, a dual inhibitor of dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN), ameliorates experimental autoimmune encephalomyelitis in SJL/J mice Biol Chem392: 233-7
Reinhold D, Bank U, Entz D, Goihl A, Stoye D, Wrenger S, Brocke S, Thielitz A, Stefin S, Nordhoff K, Heimburg A, Tager M, Ansorge S (2011) Biol Chem392: 233-7