Multiple Sclerosis (MS) is a serious autoimmune disease. The patient in an advanced state of the disease has restrained mobility and remains handicapped. It is therefore understandable that there is a great need for novel drugs and vaccines for the treatment of MS.
Multiple Sclerosis (MS) is a serious systemic demyelinating disease that leads to the partial paralysis of the patient who needs the assistance of medicare in order to survive with low quality of life. The need for an effective treatment in the form of medication or vaccine is more urgent than ever before . This chronic inflammatory and neurodegenerative disease is initiated by autoreactive T helper (Th) cells and affects approximately 2.5 million people worldwide. Thus, there is an urgent need to develop effective treatments. Advances in the immunotherapy of MS have been recently reported in excellent reviews . The pathogenesis of MS has been extensively studied over the last years, which shows a complex immunological involvement. Myelin epitopes have been identified as a target for autoimmune CD4+ T cells and antibodies, and much focus has been around the modulation of Th1 pro-inflammatory autoreactive CD4+ T cells against myelin epitopes, namely myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG) .
|Peptide Analog [Reference]||Major Effects|
|MBP83–99 and PLP139–151 ||These agonist peptides are involved in the pathophysiology of MS and also induce EAE in animal models.|
|MBP82–98 ||Dirucotide in animal models inhibits disease and in early human clinical trials showed efficacy; however, the peptide did not meet primary endpoints in phase III-trials.|
|cyclic(87–99)[MBP87–99] ||Stimulates Th2 cytokines and inhibits EAE in mice.|
|MBP87–99(R91,A96), MBP87–99(A91,A96) ||Induces IL-4 and antagonizes IFNγ responses in mice.|
|MBP72–85 ||These agonist peptides induce EAE in mice and Th1 responses in humans.|
|MBP72–85(A79) ||Suppresses EAE in mice.|
|PLP139–151(L144, R147) ||Antagonizes PLP-specific T-clones in vitro.|
|cyclic-MBP82–98||Exerts strong binding to the HLA-DR2 and lowers binding to the HLA-DR4 allele in vitro|
|cyclic-MBP87–99(A96) or (R91A96) ||Suppresses proliferation of CD4+ T cells and exerts IL-10 selectivity in vitro. Binds to HLA-DR4 and is stable to lysosomal enzymes and cathepsins B, D, and H.|
linear and cyclic-MBP83–99(A91,A96) 
Mannan-linear and cyclic-MBP83–99(A91,A96) 
|Reduces EAE, demyelination, and chronic axonopathy in acute and chronic phases of EAE in mice.
Low disease burden in regards to EAE in mice with minimal inflammatory, demyelinating, and axonopathic pathology compared to its linear counterpart.
Decreases IFNγ responses in mice.
Diverts the “bad” IFNγ to “good” IL-4 cytokine in mice.
|Mannan-MOG35–55 ||Protects mice against EAE in prophylactic and therapeutic protocols, with oxidized-conjugated peptides giving the best results.|
|Decreases Th1 responses.
Shifts Th1 responses to Th2 responses.
|Induces T-cell proliferation and IFNγ secretion in mice.
Activates T cells and increases IFNγ secretion in mice.