Therapeutic effect of mbp immunodominant peptides encapsulated in nanovehicles in the development of experimental autoimmune encephalomyelitis in DA rats

• Published in: Russian journal of bioorganic chemistry Vol. 38; no. 3; pp. 266 - 273
• Main Authors: Stepanov, A. V., Belogurov, A. A., Mamedov, A. E., Melamed, D., Smirnov, I. V., Kuzina, E. S., Genkin, D. D., Boyko, A. N., Sharanova, S. N., Bacon, A., Ponomarenko, N. A., Gabibov, A. G.
• Format: Journal Article
• Language: English
• Published: Dordrecht SP MAIK Nauka/Interperiodica 01.05.2012
• Subjects: Animal models; Autoantibodies; Autoantigens; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Dopamine; Epitopes; Experimental allergic encephalomyelitis; Life Sciences; Liposomes; Mimicry; Multiple sclerosis; Myelin basic protein; Neurodegenerative diseases; Oligodendrocytes; Organic Chemistry; Pharmacology; myelin basic protein; liposome technology; glatiramer acetate; experimental autoimmune encephalomyelitis (EAE); multiple sclerosis
• ISSN: 1068-1620; 1608-330X
• DOI: 10.1134/S1068162012030144

Multiple sclerosis (MS) is a severe autoimmune neurodegenerative disease. It attacks mainly young people. The development of new approaches to MS treatment is a challenge to modern immunology and pharmacology. In the present study, a high therapeutic efficacy of immunodominant peptides of myelin basic protein (MBP) incorporated into unilamellar mannosylated liposomes in the development of experimental autoimmune encephalomyelitis (EAE) is demonstrated in DA rats. MBP is a component of the oligodendrocyte membrane, which forms the axonal sheath. This protein is among the major autoantigens in MS. We have analyzed the binding pattern of anti-MBP autoantibodies from MS patients using a previously designed MBP epitope library. Utilizing the same approach, we have investigated the pool of anti-MBP antibodies from SJL/J and C57BL/6mice and DA rats with EAE. According to the autoantibody binding patterns, the rodent model most closely mimicking MS is EAE in DA rats. We have chosen three immunodominant MBP fragments encapsulated in unilamellar mannosylated liposomes for the treatment of the verified DA rodent model. MBP fragment 46–62 is the most efficient in mitigating the first EAE attack, whereas MBP 124–139 and 147–160 inhibit the development of pathology at the regression stage. Simultaneous administration of these peptides in liposomes significantly reduces the level of antibodies against MBP. The synergistic therapeutic effect of MBP fragments reduces the integral disease score by inhibiting the first EAE attack and mitigating the subsequent relapse. Thus, our findings offer new opportunities for the efficient treatment of multiple sclerosis.