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.
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Authors | Dirk Reinhold, Ute Bank, Dominik Entz, Alexander Goihl, Diana Stoye, Sabine Wrenger, Stefan Brocke, Anja Thielitz, Sofia Stefin, Karsten Nordhoff, Anke Heimburg, Michael Täger, Siegfried Ansorge |
Journal | Biological chemistry
(Biol Chem)
Vol. 392
Issue 3
Pg. 233-7
(Mar 2011)
ISSN: 1437-4315 [Electronic] Germany |
PMID | 21194377
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Dipeptidyl-Peptidase IV Inhibitors
- Protease Inhibitors
- DNA
- CD13 Antigens
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Topics |
- Animals
- CD13 Antigens
(antagonists & inhibitors)
- Cell Line
- DNA
(biosynthesis)
- Dipeptidyl-Peptidase IV Inhibitors
(therapeutic use)
- Disease Models, Animal
- Encephalomyelitis, Autoimmune, Experimental
(drug therapy, immunology)
- Humans
- Lymphocyte Activation
(drug effects)
- Mice
- Mice, Inbred Strains
- Protease Inhibitors
(therapeutic use)
- T-Lymphocytes
(drug effects)
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