Novel Nanoparticle Drugs Suppress Wide Range of Autoimmune Conditions

A novel class of drugs comprising nanoparticles coated with disease relevant peptide-major histocompatibility complexes (pMHCs) coverts pathogenic T-lymphocytes into disease-specific regulatory T-cells, which suppress all other lymphocytes participating in the autoimmune disease process without compromising systemic immunity.

Regulatory T-cells hold promise as targets for therapeutic intervention in autoimmunity, but approaches capable of expanding antigen-specific regulatory T-cells in vivo have not been available. This situation may be changing, as investigators at the University of Calgary (Alberta, Canada) and the biotech company Parvus Therapeutics Inc. (Calgary, Canada) have developed a novel class of drugs called Navacims, which are able to initiate the generation and expansion of antigen-specific regulatory CD4+ T cell type 1 (TR1)-like cells in different mouse models.

Navacims operate by directly binding to pathogenic antigen-specific T-lymphocytes via their antigen receptors and by reprogramming these cells to become disease-specific regulatory T-cells. These TR1-like cells suppress autoantigen-loaded antigen-presenting cells and drive the differentiation of cognate B-cells into disease-suppressing regulatory B-cells, without compromising systemic immunity.

Results published in the February 17, 2016, online edition of the journal Nature revealed that Navacims designed to target T-cells in newly diabetic nonobese (NOD) mice restored normal blood sugar regulation in the majority of the mice tested. In another trial, Navacims restored motor function to paralyzed C57BL/6 mice with acute experimental autoimmune encephalomyelitis (a model of multiple sclerosis). In addition, Navacims that targeted disease-causing T-cells in joints resolved joint swelling and destruction in arthritic mice.

Senior author Dr. Pere Santamaria, CSO of Parvus Therapeutics, said, "Autoimmune diseases, including type I diabetes, multiple sclerosis, and rheumatoid arthritis, are extraordinarily complex responses of our immune system against some of our own tissues (e.g., pancreas, brain and joints, respectively), leading to chronic organ inflammation, organ dysfunction, and, in some cases, premature death. Blunting these incompletely understood immune responses without suppressing the normal components of our immune system that protect us against infection and cancer is not currently possible."

"However, our work offers a pharmaceutical solution to this fundamental problem," said Dr. Santamaria. "Navacims essentially re-program disease-causing white blood cells to become disease-suppressing cells, known as regulatory cells, leading to sustained therapeutic effects in various spontaneous and experimental autoimmune diseases, as reported in our article in. Essentially, we have found that Navacims can be tailored to treat a wide range of autoimmune diseases, while sharing a common structure. Importantly, they have been shown to affect human white blood cells in the same manner as they do murine cells. Furthermore, Navacims have shown promising safety findings in preclinical in vivo models. Based on our results to date, we believe Navacims represent a therapeutic platform with broad-ranging health care implications."

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University of Calgary
Parvus Therapeutics Inc.