The purpose of this study was to find an appropriate solution in reducing inflammation around the ankle joint for Rheumatoid Arthritis (RA) patients, so they are able to increase their endurance and improve their overall quality of life. RA patients have to deal with a significant amount of complications that…
The purpose of this study was to find an appropriate solution in reducing inflammation around the ankle joint for Rheumatoid Arthritis (RA) patients, so they are able to increase their endurance and improve their overall quality of life. RA patients have to deal with a significant amount of complications that include chronic inflammation, continuous pain in their joints, and overwhelming stress. In addition, it is very common for RA patients to develop severe mental issues that only makes matters worse. As a result, it is imperative that treatments are provided to RA patients to improve their current situation. Three devices from the current market, made for reducing inflammation of the ankle, were chosen for evaluating the effectiveness of each device. It was determined that with 95% confidence that the Gonicc Professional Foot Sleeve was the most effective in reducing inflammation. A prototype was developed based on the feedback of the participants. Further improvements, the prototype will be compared against the Gonicc Professional Foot Sleeve to determine which is the best solution to improve millions of RA patients' lives.
Autoimmunity develops when the immune system targets self-antigens within the body. Rheumatoid arthritis (RA) is a common autoimmune disease, and its progression is characterized by pro-inflammatory immune cells rapidly proliferating, migrating, and infiltrating joint tissue to provoke inflammation. In order to fulfill this taxing autoreactive response, an increase in energy…
Autoimmunity develops when the immune system targets self-antigens within the body. Rheumatoid arthritis (RA) is a common autoimmune disease, and its progression is characterized by pro-inflammatory immune cells rapidly proliferating, migrating, and infiltrating joint tissue to provoke inflammation. In order to fulfill this taxing autoreactive response, an increase in energy metabolism is required by immune cells, such as dendritic cells (DCs). Therefore, a shift in DC energy reliance from the Krebs cycle toward glycolysis occurs. This metabolic shift phenotypically transitions DCs from anti-inflammatory properties toward an aggressive pro-inflammatory phenotype, in turn activating pro-inflammatory T cells and promoting RA pathogenesis. If the disease persists uncontrollably, further complications and eventual joint dysfunction can occur. Although, clinically approved drugs can prevent RA progression, they require frequent administration for temporary symptom relief. Furthermore, current approved biological products for RA are not known to have a direct modulatory effect on immunometabolism. Given that cellular metabolism controls immune cell function, this work aims to harness perturbations within RA immune cell energy metabolism and utilizes it as a therapeutic target by reprogramming immune cell metabolism via the delivery of metabolite-based particles. The two-time delivery of these particles reduced RA inflammation in a RA collagen-induced arthritis (CIA) mouse model and generated desired responses with long-term effects. Specifically, this work was achieved by:
Aim 1 – developing and delivering metabolite-based polymeric microparticles synthesized from the Krebs cycle metabolite, alpha-ketoglutarate (aKG; termed paKG MPs) to DCs to modulate their energy metabolism and promote anti-inflammatory properties (in context of RA).
Aim 2 – exploiting the encapsulation ability of paKG MPs to inhibit DC glycolysis in the presence of the CIA self-antigen (collagen type II (bc2)) for the treatment of RA in CIA mice. Herein, paKG MPs encapsulating a glycolytic inhibitor and bc2 induce an anti-inflammatory DC phenotype in vitro and generate suppressive bc2-specific T cell responses and reduce paw inflammation in CIA mice.
