Emerging Concepts in MS: MRI measure as an indicator of potential conversion to SPMS, novel therapeutic targets of neuroinflammation, and roles of biological measures of aging in MS

Presenters at the emerging concepts in MS session at the ACTRIMS 2019 Forum deliver results on novel research areas in MS. At the session, we heard about a potential new way to identify individuals that may be at risk of progression from relapsing-remitting MS (RRMS) to secondary-progressive MS (SPMS), a new target that may prevent inflammation in MS, and an aging-related mechanism that could be a novel therapeutic strategy in MS.

1. Spinal cord atrophy linked to conversion from RRMS to SPMS

Current therapies attempt to suppress inflammatory activity, however, a significant number of people still progress from RRMS to SPMS.  Magnetic Resonance Imaging (MRI) measures provide useful information about disease progression and disability. Dr. Antje Bischof from the Weill Institute for Neurosciences, University of California, San Francisco, utilized MRI to determine if spinal cord atrophy could correlate to conversion from RRMS to SPMS. In a 12-year observational study, Dr. Bischof compared imaging outcomes in 54 individuals with RRMS who converted to SPMS to 54 individuals that remained with RRMS and to 54 age- and sex-match non-MS controls.  Individuals that progressed to SPMS showed accelerated rates of spinal cord atrophy compared to individuals that remained with RRMS and non-MS controls. There was no difference between the groups on lesion and brain volumes. The data presented by Dr. Bischof indicates that the rate of tissue loss at the cervical spinal cord could be an indicator of conversion to SPMS.

2. Nlrx1 as a novel therapeutic target to prevent inflammation in MS

Many of the current treatments for MS work by either preventing immune cells from migrating into the brain and spinal cord, collectively called the central nervous system (CNS), or depleting the immune response. Anti-inflammatory molecules that are already present in the CNS can potentially be therapeutic targets that slow the progression of MS. Dr. Marjan Gharagozloo, funded by the MS Society for her doctoral work from the University of Sherbrooke, presented her research on investigating a molecule, called Nlrx1, which is found in the mitochondria (the powerhouse of the cell). Specifically, Dr. Gharagozloo examined if Nlrx1 alters MS in an animal model of the disease. Mice without the Nlrx1 rapidly progressed in their MS compared to mice with the Nlrx1 gene. Furthermore, Dr. Gharagozloo observed infiltration of inflammatory cells into the spinal cord in mice without Nlrx1. Nlrx1 was found to also prevent the generation of inflammatory cells in the CNS that are known to trigger the activation of immune cells in the body in an animal models of MS. While additional work is needed to unravel its complete role, Nlrx1 could be a potential therapeutic target that prevents CNS inflammation in MS.

3. Targeting aging mechanisms as a therapeutic strategy for MS

Aging is a factor that has been linked to influencing the course of MS, specifically through changes in disability progression and neurodegeneration. Dr. Kristen Krysko from the University of California, San Francisco, investigated whether a biological marker associated with aging, called leukocyte telomere length (LTL), is linked to disability progression and change in brain volume in people with MS. In a study with a cohort of 365 women and 160 men with MS or clinically isolated syndrome (CIS), Dr. Krysko measured the length of LTL, performed MRI, and examined changes in disability. The results showed that a higher age and disease duration was associated with shorter LTL. Furthermore, individuals with shorter LTL had greater disability and lower brain volumes. The research sheds light on a potential new measure for disability progression and also a target for therapeutic strategies in MS. 

Have any questions/comments on some of the emerging concepts in MS? Leave them below.

Remember to stay tuned to @Dr_KarenLee for live updates on the #ACTRIMS conference. 

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