Utilizing Methotrexate and Dimethyl fumarate on the STING Pathway Modulation to Alleviate Symptoms of Crohn's Disease
Shaurya Patni
Massachusetts Academy of Math and Science, Worcester, USA
Publication date: December 25, 2024
Massachusetts Academy of Math and Science, Worcester, USA
Publication date: December 25, 2024
DOI: http://doi.org/10.34614/JIYRC202445
ABSTRACT
An autoimmune disease results from the immune system accidentally attacking the body instead of protecting it and is often treated through immunosuppressive drugs. Crohn’s disease induces inflammation in the gastrointestinal tract, hindering nutrient absorption and resulting in excessive diarrhea, ulcers, and abdominal discomfort. The inflammation also creates opportunities to activate the STING pathway. The STING pathway releases proinflammatory chemokines and cytokines in the digestive system, causing damage to the gastrointestinal lining. This project aims to find therapeutic agents that inhibit the cGAS-STING pathway, which is linked with inducing inflammation in Crohn’s disease. Methotrexate (MTX) and Dimethyl fumarate (DMF) effectively inhibited the pathway when utilizing pro-inflammatory ELISAs, quantitative PCR, and a bone marrow-derived macrophage cell line. In the ELISA test, DMF significantly inhibited IFNβ and IL-6 production, while MTX was only effective for IFNβ, suggesting that DMF can target different steps of the pathway. The drug's novel application in this project indicates that the STING pathway can be inhibited, reducing excessive inflammatory responses. This focused method provides a more specific treatment plan with fewer adverse effects, which is significant when considering the overall immunosuppressive effects of existing medicines. The next steps include assessing long-term adaptability, evaluating therapy side effects, and conducting immunogenicity assessments.
An autoimmune disease results from the immune system accidentally attacking the body instead of protecting it and is often treated through immunosuppressive drugs. Crohn’s disease induces inflammation in the gastrointestinal tract, hindering nutrient absorption and resulting in excessive diarrhea, ulcers, and abdominal discomfort. The inflammation also creates opportunities to activate the STING pathway. The STING pathway releases proinflammatory chemokines and cytokines in the digestive system, causing damage to the gastrointestinal lining. This project aims to find therapeutic agents that inhibit the cGAS-STING pathway, which is linked with inducing inflammation in Crohn’s disease. Methotrexate (MTX) and Dimethyl fumarate (DMF) effectively inhibited the pathway when utilizing pro-inflammatory ELISAs, quantitative PCR, and a bone marrow-derived macrophage cell line. In the ELISA test, DMF significantly inhibited IFNβ and IL-6 production, while MTX was only effective for IFNβ, suggesting that DMF can target different steps of the pathway. The drug's novel application in this project indicates that the STING pathway can be inhibited, reducing excessive inflammatory responses. This focused method provides a more specific treatment plan with fewer adverse effects, which is significant when considering the overall immunosuppressive effects of existing medicines. The next steps include assessing long-term adaptability, evaluating therapy side effects, and conducting immunogenicity assessments.
