Therapeutic nanoparticle of the AvrA protein for the treatment of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis.
- AvrA protein, at 33 kilodaltons, is approximately one-fifth the molecular weight of current antibody-based biologics.
- Use of uniform protein nanoparticles improves cellular uptake compared to existing biologics.
- Potential therapeutic with less severe side effects compared to biologics and corticosteroids.
- Has potential for oral or rectal delivery.
Approximately 1.4 million individuals in the US and 2.2 million individuals in Europe suffer from IBD. Currently there is no cure and IBD usually requires lifetime treatment. The most common treatment for IBD is mesalazine, a small molecule that acts as an inflammatory suppressant. Although mesalazine has a low incidence of systemic side effects, its therapeutic effectiveness in patients with Crohn’s disease is doubted and controversial. Other therapies on the market for inflammatory bowel diseases are biologics that have extreme side effects and carry black box labels due to increased susceptibility to serious infections.
AvrA is a 33 kilodalton protein that is produced by the bacteria Salmonella typhimurium, a pathogen that is a major cause of human gastroenteritis. The AvrA protein inhibits the NF-kappaB and JNK MAPK pathways, thereby suppressing inflammatory and apoptotic responses. It is thought that this function allows the bacteria to infect cells while simultaneously suppressing the immune and apoptotic activity of the host. Emory researchers have formulated AvrA protein into nanoparticles with diameters of ~100 nm. This nanoscale size is optimized for delivery into the intestinal epithelia. Specifically, the nanoparticles are produced by the use of a chemical crosslinking agent. The compound contains a central disulfide bond that, when reduced inside cells, can release the individual proteins. These AvrA protein nanoparticles therefore serve as both the therapeutic and the delivery vehicle. Studies show that AvrA nanoparticles reduce inflammation in mouse models of acute inflammation and colitis in vivo.
In vivo proof-of-principle study completed. Data from mouse models of inflammation show reduced inflammation and suggest potential therapeutic efficiency.
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