Therapeutic effect of encapsulated into the nanocontainers MBP immunodominant peptides on EAE development in DA rats

• Published in: Bioorganicheskaia khimiia Vol. 38; no. 3; p. 306
• Main Authors: Stepanov, A V, Belogurov, A A, Mamedov, A É, Melamed, D, Smirnov, I V, Kuzina, E S, Genkin, D D, Boĭko, A N, Sharanova, S N, Bacon, A, Ponomarenko, N A, Gabibov, A G
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 01-05-2012
• Subjects: Adult; Amino Acid Sequence; Animals; Autoantibodies - immunology; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Guinea Pigs; Humans; Immunodominant Epitopes - administration & dosage; Immunodominant Epitopes - immunology; Immunodominant Epitopes - therapeutic use; Liposomes; Mice; Mice, Inbred C57BL; Middle Aged; Molecular Sequence Data; Multiple Sclerosis - drug therapy; Myelin Basic Protein - administration & dosage; Myelin Basic Protein - immunology; Myelin Basic Protein - therapeutic use; Nanocapsules - administration & dosage; Nanocapsules - chemistry; Peptide Fragments - administration & dosage; Peptide Fragments - immunology; Peptide Fragments - therapeutic use; Rats; Rats, Inbred Strains
• ISSN: 0132-3423

Multiple Sclerosis (MS) is a serve autoimmune neurodegenerative disease. Development of innovative approaches of MS treatment is of a high priority in the modern immunology and pharmacy. In the present study we showed high therapeutic efficiency of immunodominant peptides of myelin basic protein (MBP) incorporated into the monolayer mannosylated liposomes on the development of experimental autoimmune encephalomyelitis (EAE) in DA rats. MBP is a component ofoligodendrocytes' membrane, which form axonal sheath, and is one of the major autoantigens in MS. We analyzed binding pattern ofanti-MBP autoantibodies from MS patients using previously designed MBP epitope library. Utilizing the same approach we investigated pool of anti-MBP antibodies from SJL/J and C57/BL6 mice and DA rats with induced EAE. The most relevant rodent model to MS was EAE in DA rats according to the autoantibodies' binding pattern. We selected three immunodominant MBP fragments encapsulated in monolayer mannosylated liposomes for the following treatment of verified DA rodent model. MBP fragment 46-62 was the most effective in reducing of the first EAE attack, whereas MBP 124-139 and 147-160 inhibited development of pathology during remission stage. Simultaneous administration of these peptides in liposomes significantly decreased level of anti-MBP antibodies. Synergetic therapeutic effect of MBP fragments reduced integral disease score by inhibiting first EAE wave and subsequent remission, thus, our findings disclosure novel approaches for efficient treatment of Multiple Sclerosis.