A team of researchers at Trinity College Dublin have published a study on multiple sclerosis (MS) that has uncovered evidence that a key immune system switch, known as the NLRP3 inflammasome, may play a significant role in the inflammatory processes associated with the pathogenesis of MS. This re- search emphasises that this key immune system switch should be targeted with new medicines in MS.
MS is the most common cause of pro- gressive neurological disability in young adults, preferentially affecting women between 20 and 40 years of age. Some 2.8 million people have MS worldwide, and over 9,000 people in Ireland currently have an MS diagnosis.
Onset and progression of MS is variable among individuals, and hence the disorder is broadly classified into three subtypes based solely on clinical phenotyping: (i) Relapsing remitting MS (RRMS); (ii) secondary progressive MS (SPMS); and (iii) primary progressive MS (PPMS).
Currently, there is no cure for MS, and a range of therapies are available to sup- press inflammation in MS, however, there is a pressing need for new medicines, as approved medications for MS often have a limited ability to block disability progression, and are commonly linked to side-effects.
The researchers took an innovative approach in this study by examining both brain tissue from individuals who had MS, alongside conducting an assessment of immune cells isolated from blood samples from people living with different subtypes of the disorder.
Key findings include:
- Inflammasome genes are upregulated in the brains of people with primary progressive MS, but not secondary progres- sive MS. This is particularly evident in active lesions in the brain.
- Immune cells isolated from people with MS are particularly reactive in terms of NLRP3 activation.
- Immune cells isolated from people with MS secrete higher levels of the inflammatory cytokine interleukin1?, which is closely associated with NLRP3 activation, when compared to immune cells from healthy volunteers.
- The research suggests that the expres- sion of NLRP3 inflammasome components is dysregulated in MS, both in the brain and in immune cells.
Speaking on the research, Dr Eric Downer, Associate Professor and Associate Director of Research, School of Medicine, Trinity College and lead author, said: “This work builds on previous research from my lab demonstrating the role of innate immune inflammation in MS. We took the approach of assessing the NLRP3 inflammasome both centrally and peripherally in MS, by employing the use of brain tissue samples and immune cells. Overall, we believe that our research further highlights that the NLRP3 inflammasome warrants full investigation in MS and may be a promising potential target for future MS therapies.”
