A randomized, subject and rater-blinded, placebo-controlled trial of dimethyl fumarate for obstructive sleep apnea

Abstract

ClinicalTrials.gov, NCT02438137, https://clinicaltrials.gov/ct2/show/NCT02438137?term=NCT02438137&rank=1.

Plasma APRIL as a Potential Biomarker in the Diagnosis of Obstructive Sleep Apnea

“…Meanwhile, immune cells dominate early atherosclerotic lesions, their effector molecules accelerate inflammation and NF-KB activity, which can elicit atherosclerotic lesions rupture and trigger the acute onset of arterial thrombosis [30,31]. Several studies have shown that treating OSA with continuous positive airway pressure improves inflammation and reduces of NF-KB signaling [20,32]. Even in patients with OSA who were free of overt cardiovascular disease, the physiological perturbations of inflammation and NF-KB-dependent inflammatory pathways activation often caused blood pressure and heart rate elevations, ventricular failure, myocardial infarction, and stroke [4,33].…”

“…Several studies have indicated that the relationship of APRIL and NF-KB signaling pathway activation is one of a complex interactive, APRIL could induce inflammatory activation by the activation of NF-KB signaling pathway [15,16], and conversely, NF-KBdependent pathways can influence APRIL secretion [17,18]. A large body of evidence, including experimental and clinical studies, have demonstrated that the activation of NF-KB-dependent inflammatory pathways by intermittent hypoxia and reoxygenation in OSA may be an important molecular mechanism of cardiovascular complication [4,19,20]. Moreover, both RNA and protein expression of APRIL have been shown in human plaque lymphocytes and macrophages and plasma [37,38].…”

“…Current evidence suggests that APRIL could induce inflammatory activation by the activation of NF-KB signaling pathway [15,16], and conversely, NF-KB-dependent signaling pathways, in turn, can influence APRIL secretion [17,18]. The activation of NF-KB-dependent inflammatory pathways by intermittent hypoxia and reoxygenation in OSA may be an important molecular mechanism of cardiovascular complication [4,19,20]. In addition, several studies showed that monocyte chemotactic protein-1 (MCP-1) and Lselectin as inflammation mediators can be regulated via the activation of NF-KB signaling pathways, and they were significantly elevated in patients with OSA [21][22][23][24].…”

Current Landscape of NRF2 Biomarkers in Clinical Trials

“…Such action likely precludes the use of DMF in any disease prevention settings. A summary of clinical trials utilizing fumaric acid esters, all of which include DMF, is listed in Table S1 [ 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ].…”

“…Understanding the molecular links between these two signaling pathways may lead to more informative biomarkers. Intracellular NF-κB signaling molecules have been examined to evaluate responses for inflammatory disease in clinical studies using DMF and BARD-Me [ 50 , 66 ]. Other molecular mechanisms behind Nrf2-mediated anti-inflammatory effects have been described, such as transcriptional suppression of proinflammatory cytokine genes ( Il-6 and Il-1β ) [ 227 ] and the correlation between Nrf2 signaling and NLRP3 inflammasome activity [ 228 ].…”