Grant: Team Grant: Neuroinflammation

This proposal is founded on the discovery of a new paradigm in the treatment of autoimmune disease (caused by the white blood cells of the immune system) of potential groundbreaking significance. Traditionally, vaccines have been used to expand white blood cells capable of affording protection against viruses, bacteria or cancer, or to delete white blood cells capable of causing autoimmune diseases like multiple sclerosis (MS), diabetes, and others. We have developed a 'vaccine' based on nanotechnology (using extremely tiny particles, several thousand times smaller than a typical cell) that can blunt anti-self immune responses by selectively expanding what we call 'autoregulatory' white blood cells (known as T-lymphocytes). These constitute a new type of 'autoreactive' white blood cells whose function is to put the brakes on the disease-causing autoimmune attack. Our nanomedicines can expand this population of white blood cells, enhancing their disease-countering effects, and blunt autoimmune responses without causing generalized suppression of the immune system. This proposal is an effort to advance an MS-specific nanomedicine for the treatment of central nervous system nflammation towards clinical trials, by focusing on relapsing-remitting MS patient samples, a severe autoimmune disease for which current therapies rely on systemic immunosuppression and are not curative. This will be done by testing 8 different nanomedicines with high population coverage in a novel assay system using mice transplanted with peripheral blood lymphocytes from patients. We show that treatment of such animals with disease-specific nanomedicines leads to the expansion of of the same type of disease suppressor white blood cells that resolve neuroinflammation in mouse models of MS. This work is poised to identify MS-specific nanomedicines predicted to work in early stage clinical trials, hence reducing the drug development risks and facilitating clinical translation.