Transcription Factor Analysis of SLE
Abstract
Rationale The immune system normally fights infections, but the immune system can turn against the body and attack it because it confuses it for something foreign. This is the basis for autoimmunity, and there are many autoimmune diseases, including systemic lupus erythematosus (SLE). SLE is a chronic disease that can have disease flares alternating with periods of mild symptoms; however, generally, once a person has SLE, they have it the rest of their life. There is no cure currently, and management is focused on keeping the immune system as quiet as possible. According to the Lupus Foundation of America, at least 1.5 million Americans are living with lupus, but many cases go undiagnosed. It is often called the great imitator because it can appear in so many guises. Objective Our objective is to look at SLE in a new way and to work toward a cure by not just suppressing the immune system to keep it quiet, but to target the root of the disease. We think one of the reasons the disease perpetuates is that the very chromosomes and DNA within the cells of the immune system get tangled up so the cell misbehaves. This type of study is called epigenetics and this field is in its infancy, but we think it shows great promise to take a chronic debilitating autoimmune disease and re-set the immune system so that it functions properly again. In this study, we will examine the DNA from different cell types and find the crux of the problem to develop new therapeutics. Aims Our first approach will be to look at the chromosomes in SLE and find the keys that will unlock the altered structure. We will then look at the effect of targeting those keys, with a goal of changing the chromosomes back to the healthy state. Impact There are now over 50 drug trials looking at different ways to suppress the immune system as a treatment for SLE. These all conceptually hinge on the concept of keeping the inflamed, abnormal immune system quiet and all have as a side-effect an increased risk of infection, the major cause of death in early SLE. Our ultimate aspiration is to cure this chronic disease. Our approach is novel and looks at the disease in a new way with goal of re-setting the immune system. It is aspirational and risky but offers a new insight for a disease where progress has been limited in the past 20 years, with only one new drug for SLE approved by the Food and Drug Administration. With 1.5 million Americans living with this chronic disease, that is inadequate. A new approach and loftier goals than immune suppression are critically needed.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910562
Entities
People
- Kathleen Sullivan
Organizations
- Children's Hospital of Philadelphia
- United States Army