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.
