Multiple Sclerosis (MS) is a chronic and potentially disabling disease of the central nervous system (CNS) in which the immune system attacks the protective myelin layer that surrounds nerve cells. While the majority of individuals diagnosed with MS initially present with a non-progressive relapsing form of the disease, there is significant risk of eventually transitioning to a more progressive form for which there are few effective treatments. Consequently, early intervention with disease-modifying therapies (DMTs) is essential for effective disease management. Newly diagnosed patients are typically started on one of four first-line therapies (beta interferon, glatiramer acetate, teriflunomide, or dimethyl fumarate). Though there are distinct differences between these treatments in regard to efficacy and safety, there is no uniform standard for making decisions about which to initiate treatment with. This review gives an overview of current first-line MS therapies, and seeks to highlight the lack of comparison data and the gaps in the current understanding of disease management, as well as the need for more comprehensive research in these areas.

PURPOSE: Previous work suggests that Dihydroorotate dehydrogenase (DHODH) inhibition via teriflunomide (TERI) may provide protection in multiple disease models. To date, little is known about the effect of TERI on the heart. This study was performed to assess the potential effects of TERI on cardiac ischemia reperfusion injury. METHODS: Male and female rat hearts were subjected to global ischemia (25 min) and reperfusion (120 min) on a Langendorff apparatus. Hearts were given either DMSO (VEH) or teriflunomide (TERI) for 5 min prior to induction of ischemia and during the reperfusion period. Left ventricular pressure, ECG, coronary flow, and infarct size were determined using established methods. Mitochondrial respiration was assessed via respirometry. RESULTS: Perfusion of hearts with TERI led to no acute effects in any values measured across 500 pM-50 nM doses. However, following ischemia-reperfusion injury, we found that 50 nM TERI-treated hearts had an increase in myocardial infarction (p < 0.001). In 50 nM TERI-treated hearts, we also observed a marked increase in the severity of contracture (p < 0.001) at an earlier time-point (p = 0.004), as well as reductions in coronary flow (p = 0.037), left ventricular pressure development (p = 0.025), and the rate-pressure product (p = 0.008). No differences in mitochondrial respiration were observed with 50 nM TERI treatment (p = 0.24-0.87). CONCLUSION: This study suggests that treatment with TERI leads to more negative outcomes following cardiac ischemia reperfusion, and administration of TERI to at-risk populations should receive special considerations.