Development of inflammasome assays to assess novel therapeutics in immune cells related to multiple sclerosis pathogenesis

Multiple sclerosis (MS) is a chronic autoimmune disorder associated with sensory and motor impairments. In Ireland, MS currently afflicts over 9,000 people, with approximately 290 people diagnosed with MS in Ireland each year. A range of disease-modifying therapies (DMTs) are available for symptom management in MS, nevertheless, most DMTs present with side-effects. There is a need for new therapeutic strategies in MS. Although MS is a complex disease, there is evidence indicating the role of neuroinflammation in MS pathogenesis. The NLRP3 inflammasome has a well-established function in innate immunity, and current evidence suggests that targeting the inflammasome is a key therapeutic target in the disease. Indeed, small molecule NLRP3 inhibitors are in pre-clinical development for MS. The goals of this project are to define the role of the inflammasome in MS and to identify novel inflammasome inhibitors that have efficacy in immune cells with relevance to MS. This study assessed the expression profile of inflammasome markers (IL- 1β/IL-18) in plasma samples from healthy control cases and people with MS. In addition, using a combination of human macrophage cell lines (THP-1), primary immune cell lines and whole blood assays, this project has established inflammasome assays. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are protective in murine models of MS, and Sativex (a 1:1 combination of THC:CBD), is clinically available for symptom management in MS. Hence, this project is assessing the efficacy of THC/CBD as inflammasome inhibitors in immune cells with relevance to MS.

Publikationsverlauf

Artikel online veröffentlicht:
16. November 2023