Immune modulating peptides for the treatment and suppression of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a neurodegenerative disease in which the immune system recognizes proteins of the myelin sheath as antigenic, thus initiating an inflammatory reaction in the central nervous system. This leads to demyelination of the axons, breakdown of the blood-brain barrier, and lesion formation. Current therapies for the treatment of MS are generally non-specific and weaken the global immune system, thus making the individual susceptible to opportunistic infections. Antigenic peptides and their derivatives are becoming more prevalent for investigation as therapeutic agents for MS because they possess immune-specific characteristics. In addition, other peptides that target vital components of the inflammatory immune response have also been developed. Therefore, the objectives of this review are to (a) summarize the immunological basis for the development of MS, (b) discuss specific and non-specific peptides tested in EAE and in humans, and (c) briefly address some problems and potential solutions with these novel therapies.

Subcutaneous inverse vaccination with PLGA particles loaded with a MOG peptide and IL-10 decreases the severity of experimental autoimmune encephalomyelitis

“…In particular, the low frequency of these cells, their poor growth in culture, and their high functional plasticity in vivo have made their use a significant challenge. Antigen-specific strategies may potentially circumvent these limitations in vivo [10,11], but effective approaches to restore the T EFF /T REG balance in vivo remain largely undefined [9].…”

Co-Delivery of Autoantigen and B7 Pathway Modulators Suppresses Experimental Autoimmune Encephalomyelitis

“…Co-delivery of both antigen and a co-stimulatory context signal activates an antigen-specific adaptive immune response, whereas delivery of a co-inhibitory context signal or absence of either signal can render an anergic response (i.e., no response) and is believed to be a main mechanism of peripheral immune tolerance (8,9,13). Thus, co-delivery of a synthetic co-inhibitory context signal and autoantigen may be a suitable pharmacological template to restore immune tolerance and treat various autoimmune disorders (13)(14)(15)(16).…”

“…Unlike antibody-derived therapeutics that can be immunogenic, small peptide therapies are less likely to be immunogenic and offer an alternative method of inhibiting activation of self-reactive T cells and pAPCs (14). Methods employing peptides targeting different aspects of the B7 signaling pathway have been tested in animal models of RA, MS, and allograft rejection with positive results (18)(19)(20)(21).…”

“…Methods employing peptides targeting different aspects of the B7 signaling pathway have been tested in animal models of RA, MS, and allograft rejection with positive results (18)(19)(20)(21). These peptide therapies are thought to work by blocking delivery of the co-stimulatory signal from the pAPC, resulting in T cell anergy and promotion of tolerance to treat autoimmunity (14). Therapies only targeting the B7 pathway share the same drawback as most current therapies for autoimmune disease as they are prone to non-specific suppression of the immune system rendering the patient more susceptible to opportunistic infections (13,14).…”

“…These peptide therapies are thought to work by blocking delivery of the co-stimulatory signal from the pAPC, resulting in T cell anergy and promotion of tolerance to treat autoimmunity (14). Therapies only targeting the B7 pathway share the same drawback as most current therapies for autoimmune disease as they are prone to non-specific suppression of the immune system rendering the patient more susceptible to opportunistic infections (13,14). The creation of an antigen-specific treatment capable of suppressing the immune response by co-delivery of autoantigen and immune inhibitor may improve the safety and efficacy of autoimmune therapies.…”