Optimizing the Treatment of Experimental Autoimmune Encephalomyelitis via Pulmonary Delivery of Soluble Antigen Arrays

Abstract

Soluble antigen arrays (SAgAs) were used to treat experimental autoimmune encephalomyelitis (EAE), which is a mouse model for multiple sclerosis (MS). SAgAs offer a targeted therapy for MS, which is not present in current therapies. The different routes of administration, injection volume, dosing amount, and dosing schedule were explored to find that pulmonary instillation of SAgAs at 50 μL on a 200 nMol PLP basis on days 4, 7, and 10 of the study are most efficacious. With the next study, the different components of SAgAs (hyaluronic acid, PLP, LABL, and bifunctional peptide inhibitor) were also investigated via pulmonary delivery to find that PLP and SAgAs decreased the symptoms of EAE the most. PLP, HA-PLP, and SAgAs were further explored either via subcutaneous injection or pulmonary instillation to find that HA-PLP and SAgAs decreased disease progression in mice with EAE. Cytokine panels were also used to determine if tolerance was induced in these mice via the measurements of pro- and anti-inflammatory cytokines. Lastly, lung histology was explored to find signs of inflammation. Overall, SAgAs are found to be very efficacious in treating mice via PI and the presence of PLP makes a big difference. Other methods like the presence of regulatory T cells need to be used to find additional signs of tolerance induction in future studies.