Project: Advancing an antigen-specific nanomedicine for the treatment of central nervous system autoimmunity

Duration 01/02/2015 - 31/08/2018
Project Topic The complexity of autoimmune diseases is a barrier to the design of strategies that can blunt autoimmunity without impairing systemic immunity. We have shown that nanoparticles (NPs) coated with experimental autoimmune encephalomyelitis (EAE) or type 1 diabetes (T1D)-relevant peptide–MHC (pMHC) class II complexes can restore motor function and normoglycemia in paralyzed or diabetic animals, respectively. pMHC class II-NP therapy functions by expanding, in an epitope-specific manner, cognate T-regulatory-1 (TR1) CD4+ T-cells that resolve neuroinflammation and promote re-myelination of de-myelinated areas of the CNS, affording a neuroprotective effect. We have shown that any single pMHC specificity involved in any given autoimmune disease is capable, when coated as a ligand onto NPs, to blunt the autoimmune response, regardless of prevalence or role in the disease. Despite its potential significance, advancement of this new therapy to the clinic faces one fundamental barrier: the lack of human translational data. This proposal aims to overcome the above roadblock by testing the ability of MS-specific pMHC-NP compounds to expand CNS-specific TR1 cells in NOD.Scid.Il2rg-null (NSG) mice reconstituted with peripheral blood mononuclear cells and TR1 cell lines from patients with relapsing-remitting MS. Preliminary data demonstrate the feasibility of this approach. Our goal is to identify a MS-specific nanomedicine with broad population coverage for clinical development.
Call European Research Projects on Neuroinflammation

Project partner

Number Name Role Country
1 University of Calgary Coordinator Canada
2 Ospedale San Raffaele Partner Italy
3 Consorci Institut D'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) Partner Spain