Competition Catalyst Grant 2017-18

Application Metrics:  3/6 Applications Funded

Principal Investigator:  Dr. Joyce Rauch

Institution:  Research Institute of the McGill University Health Centre

Project Title:  RIPK3: A novel therapeutic target in SLE

Funding Received:  $35,000 Awarded

Project Lay Summary:  Systemic lupus erythematosus (SLE) is an autoimmune disease that affects approximately one in every 1000 Canadians, and can result in life-long suffering and premature death. Individuals with SLE develop an immune response against their own cells and tissues, resulting in autoantibodies and organ damage. Current treatments of SLE focus on suppressing the immune system in general or the B cells specifically responsible for autoantibody production. Targeted therapies affecting key pathways implicated in the development of SLE, such as cell death and inflammation, are lacking.

We have found that a single gene encoding a protein called “RIPK3” is required for the development of autoantibodies and disease in a murine model of SLE. RIPK3 is a master regulator of cell death and inflammation. We will inhibit RIPK3 therapeutically to see whether we can prevent or improve SLE disease in two models of SLE: (1) mice in which SLE is induced experimentally (environmental trigger); and (2) mice that develop SLE spontaneously (genetic trigger). Our findings will provide proof of concept that targeting

RIPK3-dependent mechanisms in murine SLE results in prevention or improvement of this chronic and debilitating disease. These data could lead to Phase I trials of new therapeutic agents targeting RIPK3-dependent mechanisms in patients with SLE.

Targeting RIPK3-dependent mechanisms in SLE is a novel innovation that can impact both knowledge and patient care, and lead to improved treatments in SLE.