title: PETIR-001, a dual inhibitor of dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN), ameliorates experimental autoimmune encephalomyelitis in SJL/J mice.
abstract: 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.
authors.affiliation: Institute of Molecular and Clinical Immunology, Otto von Guericke University Magdeburg, D-39120 Magdeburg, Germany. dirk.reinhold@med.ovgu.de
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhold
authors.forename: Ute
authors.initials: U
authors.lastname: Bank
authors.forename: Dominik
authors.initials: D
authors.lastname: Entz
authors.forename: Alexander
authors.initials: A
authors.lastname: Goihl
authors.forename: Diana
authors.initials: D
authors.lastname: Stoye
authors.forename: Sabine
authors.initials: S
authors.lastname: Wrenger
authors.forename: Stefan
authors.initials: S
authors.lastname: Brocke
authors.forename: Anja
authors.initials: A
authors.lastname: Thielitz
authors.forename: Sofia
authors.initials: S
authors.lastname: Stefin
authors.forename: Karsten
authors.initials: K
authors.lastname: Nordhoff
authors.forename: Anke
authors.initials: A
authors.lastname: Heimburg
authors.forename: Michael
authors.initials: M
authors.lastname: Täger
authors.forename: Siegfried
authors.initials: S
authors.lastname: Ansorge
mesh_terms: D000818:Animals; D018826:CD13 Antigens / Q000037:antagonists & inhibitors*; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D011480:Protease Inhibitors / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011480:Protease Inhibitors; D004247:DNA; D018826:CD13 Antigens