Type 1 diabetes (T1D) is an autoimmune disease where the body’s own immune system mistakenly destroys the insulin-producing beta cells in the pancreas. Therapies targeting this immune response have demonstrated some efficacy in preserving the secretion of insulin, but these outcomes are not generally sustained. New strategies able to create more lasting effects are therefore needed. We propose to investigate whether dimethyl fumarate (DMF) can be used as a novel therapeutic agent to prevent T1D.
DMF was recently approved by the FDA for the treatment of another autoimmune disease called relapsing-remitting multiple sclerosis. Data in the animal model of multiple sclerosis and humans have shown that DMF significantly improves clinical outcomes by targeting the immune response through several mechanisms which include the inhibition of certain aspects of cell metabolism.
Our long-term goal is to launch a clinical trial to test whether DMF preserves insulin secretion in T1D patients. As a pre-requisite to a clinical trial, we must have supportive preclinical data that demonstrates DMF’s efficacy in a disease-relevant model. We propose to conduct pre-clinical investigations in the NOD mouse model, a widely accepted model of T1D, to test whether DMF can prevent the autoimmune attack on the beta cells. This study is relevant since DMF has not been tested in T1D and yet it appears to possess many desirable properties. The proposed project represents a novel approach in treating the disease through a mechanism of action that includes metabolic inhibition and immune modulation.
The traditional drug development is a time-consuming, high-investment, and high-risk process. In this project, we will explore the possibility of repositioning an existing medication, which is already able to target autoimmunity. This study also represents a tremendous opportunity for accelerating the discovery of a new therapy for T1D.
Without Step 1 there cannot be a Step 2 or most importantly the last Step!