title: Liposome-encapsulated peptides protect against experimental allergic encephalitis.
abstract: Multiple sclerosis (MS) is a severe inflammatory and neurodegenerative disease with an autoimmune background. Despite the variety of therapeutics available against MS, the development of novel approaches to its treatment is of high importance in modern pharmaceutics. In this study, experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats has been treated with immunodominant peptides of the myelin basic protein (MBP) encapsulated in mannosylated small unilamellar vesicles. The results show that liposome-encapsulated MBP(46-62) is the most effective in reducing maximal disease score during the first attack, while MBP(124-139) and MBP(147-170) can completely prevent the development of the exacerbation stage. Both mannosylation of liposomes and encapsulation of peptides are critical for the therapeutic effect, since neither naked peptides nor nonmannosylated liposomes, loaded or empty, have proved effective. The liposome-mediated synergistic effect of the mixture of 3 MBP peptides significantly suppresses the progression of protracted EAE, with the median cumulative disease score being reduced from 22 to 14 points, compared to the placebo group; prevents the production of circulating autoantibodies; down-regulates the synthesis of Th1 cytokines; and induces the production of brain-derived neurotrophic factor in the central nervous system. Thus, the proposed formulation ameliorates EAE, providing for a less severe first attack and rapid recovery from exacerbation, and offers a promising therapeutic modality in MS treatment.
authors.affiliation: M. M. Shemyakin and Y. A. Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Belogurov
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Stepanov
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Smirnov
authors.forename: Dobroslav
authors.initials: D
authors.lastname: Melamed
authors.forename: Andrew
authors.initials: A
authors.lastname: Bacon
authors.forename: Azad E
authors.initials: AE
authors.lastname: Mamedov
authors.forename: Vitali M
authors.initials: VM
authors.lastname: Boitsov
authors.forename: Lidia P
authors.initials: LP
authors.lastname: Sashchenko
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Ponomarenko
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Sharanova
authors.forename: Alexey N
authors.initials: AN
authors.lastname: Boyko
authors.forename: Michael V
authors.initials: MV
authors.lastname: Dubina
authors.forename: Alain
authors.initials: A
authors.lastname: Friboulet
authors.forename: Dmitry D
authors.initials: DD
authors.lastname: Genkin
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Gabibov
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004660:Encephalitis / Q000209:etiology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000150:complications / Q000517:prevention & control*; D008081:Liposomes; D051379:Mice; D010455:Peptides / Q000627:therapeutic use*; D051381:Rats; D020349:Surface Plasmon Resonance
chemical_list: D008081:Liposomes; D010455:Peptides