Novel Small-Molecule Inhibitor of Tyk2: Lucrative Therapeutic Target in Lupus
Abstract
The topic of this research proposal is systemic lupus erythematosus (SLE), commonly known as lupus, in this year s Peer Reviewed Medical Research Program. Lupus is a disease of the immune system where patients suffer from damage to different organs like kidney, heart, and nervous system. In lupus, the immune system (the body s defense mechanism) starts attacking the self-tissues. According to the Lupus Foundation of America, there are 1.5 million SLE patients in America and more than 5 million patients worldwide. Lupus mostly targets young women in their child-bearing years and remains one of the major causes of heart failure in young women. There is no permanent cure for lupus, and most of the current therapies have harmful side effects. Patients have a poor quality of life, and in severe cases lupus can prove to be fatal. In lupus, a particular type of immune cell (B cells) start producing antibodies against one s own body tissue and they are the major cause of organ damage. The abnormal behavior of B cells is driven by several factors like gender, environmental factors, and inflammatory molecules called cytokines. These inflammatory molecules also cause accumulation and infiltration of white blood cells into different organs causing inflammation and enhancing organ damage. As lupus is characterized by a self-destructive immune system, current treatments rely on suppressing the immune system in general, which diminishes the ability to fight infection -- one of the biggest harmful side effects. Previous studies conducted to find novel cures for lupus has focused on inhibiting singular targets such as particular immune cell or cytokine but have failed to attain expected efficacy. This study proposes to use a single inhibitor that will target three of the most important cytokines (interferon-alpha, interleukin-6, and interleukin-23) that drive lupus. The inhibitor used in this study will simultaneously block two molecules, Tyrosine Kinase 2 (Tyk2) and Janus Kinase 1 (Jak1), which are essential for the function of lupus driving cytokines. Therefore, the proposed study will use a three-way strategy to inhibit lupus, and it has been shown in similar diseases that such approaches are more effective than single-target therapies. The results from this study will establish the potential of this inhibitor as a potential novel treatment for lupus.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610609
Entities
People
- Abhishek Trigunaite
Organizations
- SRI International
- United States Army