The NLRP3 inflammasome is a multiprotein complex that plays a pivotal role in regulating the innate immune system and inflammatory signaling. Upon activation by pathogen-associated molecular patterns (PAMPs), NLRP3 oligomerizes and activates caspase-1 which initiates the processing and release of pro-inflammatory cytokines IL-1β and IL-1 that are overproduced in many inflammatory disease conditions.
At the recent EAACI meeting, researchers presented preclinical data for the inflammasome inhibitor OLT-1177 (dapansutrile), which is being evaluated by Olatec Therapeutics LLC for the treatment of inflammatory diseases.
Research at Seoul National University has led to the identification of thiourea compounds acting as nuclear receptor RORα (RORA) agonists reported to be useful for the treatment of inflammation and metabolic diseases.
Researchers have ameliorated both monogenic and complex inflammation-driven diseases through transplantation of hematopoietic stem cells with an inserted IL-1 receptor antagonist (IL-1RA) gene. The team showed that in animal models the transplanted cells worked better than monoclonal antibodies to reduce symptoms in systemic autoinflammatory diseases (SAIDs), a group of childhood-onset, lifelong diseases that vary in severity depending on the underlying mutation, but can be life-threatening.
Glucocorticoids are very effective immunosuppressive and anti-inflammatory drugs that cause dose-limiting toxicities in brain, liver and bone preventing their use mainly in chronic disorders. Researchers from Immunext Inc. recently reported results from the therapeutic evaluation of the nontoxic glucocorticoid INX-200 with anti-inflammatory efficacy in a once-per-month injection.
The targeted delivery of optimized stem cells directly into injured tissues has been used to maximize efficacy and minimize systemic exposure. Still, despite hundreds of clinical trials evaluating mesenchymal stem cell (MSC) therapy as a treatment, clinical efficacy remains highly variable. Investigators at Case Western Reserve University have developed an optimized combination of cytokines and growth factors applied to MSCs (HXB-319).
Research at Humanwell Healthcare (Group) Co. Ltd. has led to the development of heterocyclic 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitors reported to be useful for the treatment of acute lung injury, diabetes, fibrosis, graft-vs.-host disease, heart failure, inflammatory bowel disease, alopecia and osteoporosis, among others.
Cellular mediators like cytokines that are released as a reaction to cell injury or excessive stimulation can lead to the synthesis of chemotactic eicosanoid leukotriene B4 (LTB4) among others. This mediator acts as a potent chemokine promoting migration of macrophages and neutrophils into tissues during inflammation. Researchers from CNRS, Universitat de Barcelona and colleagues reported the synthesis and evaluation of new 1,4-benzodioxine derivatives with selective LTB4 antagonism activity that led to the identification of [I] as the lead compound, which had higher affinity for LTB4 receptor with an IC50 value of 288 nM.
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