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

Abstract

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.

Spinal Cord Brain Derived Neurotrophic Factor (BDNF) Responsive Cells in an Experimental Autoimmune Encephalomyelitis (EAE) Model of Multiple Sclerosis (MS): Implications in Myelin Repair

“…There are essentially two phases of disease, an inflammatory phase involving the infiltration of active T-cells and monocytes into the CNS, followed by a second phase of disease involving immune mediated cell death of oligodendrocytes (OGs) (Namaka et al, 2011b). Due to the lack of human tissue samples, MS research has largely relied on various animal models (Lu et al, 2012, Stepanov et al, 2012 to explore the intricate cellular signaling that regulates myelin structure, function and repair. Animal models using myelin basic protein (MBP) as the antigen, characteristically activate lymphocytes that mediate an inflammatory response without demyelination (Genain and Hauser, 1996).…”

Neurobehavioral burden of multiple sclerosis with nanotheranostics

“…This nanoformulation showed a synergetic therapeutic effect, wherein disease scores were reduced showing a first EAE wave inhibition followed by subsequent remission in vivo. 108 Gold NPs encapsulated with potential antioxidant compounds epigallocatechin gallate, and α-lipoic acid were found to have strong wound healing and migration along with an increase in the antioxidant activity in vivo. This could be a future application for evaluating against MS pathology.…”