This antigen-specific microparticle therapy is a robust and highly efficacious, localized treatment for multiple sclerosis (MS) without provoking global immunosuppression. MS is the most common, potentially disabling, neurological disease typically affecting young adults. About 400,000 people in the United States and about 2.5 million worldwide are affected by MS. In MS, immune cells target and destroy the protective covering (myelin) around the nerve cells causing autoimmune demyelination, thereby causing symptoms such as numbness in the limbs that may extend to a complete inability to walk, tremors and vision loss, amongst several others. Current limited therapeutic options involve use of steroids, which can cause global immunosuppression, and other poorly tolerated, disease-modifying therapies.
Researchers at the University of Florida have developed a combinatorial dual-sized polymeric microparticles (dMP) system loaded with specific MS-relevant antigens and tolerizing agents to modulate the dendritic cells of the immune system. The combination of smaller-sized particles for intracellular delivery and larger-sized particles for extracellular delivery of agents in a controlled release manner demonstrated complete protection against disease in the mouse model of MS, namely experimental autoimmune encephalomyelitis (EAE). Importantly, this microparticle-based system provides immune modulation without global systemic immunosuppression.
Highly efficacious antigen-specific immunomodulating treatment for multiple sclerosis without global immune suppression
Researchers at the University of Florida have developed antigen-specific, tolerizing treatment for MS. This is a combinatorial dual-sized MP system (dMP), encapsulating, MS specific antigens and agents selected for their capacity to modulate DC function: both through intracellular delivery of agents in phagocytosable small MPs, and subcutaneous local deposition of agents for controlled release in MPs too large to phagocytose. Disease blocking in mouse model of MS was associated with a reduction of infiltrating CD4+ T cells, inflammatory cytokine-producing pathogenic CD4+ T cells, and activated macrophages and microglia in the central nervous system. Furthermore, CD4+ T cells isolated from dMP-treated mice were anergic in response to disease-specific, antigen-loaded splenocytes. Our findings highlight the efficacy of localized microparticle-based drug delivery to mediate antigen-specific tolerance to block MS without global immunosuppression.
