dimethyl fumarate / Generic mfg. 
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  • ||||||||||  dimethyl fumarate / Generic mfg.
    [VIRTUAL] Could Optical Coherence Tomography Be Useful To Follow The Treatment Response? () -  Mar 6, 2021 - Abstract #ACTRIMSForum2021ACTRIMS_Forum_326;    
    Consistent results were observed in the DMF-to-DRF switch subgroup. In our cohort, at baseline most of patients present a reduction of RNFL thickness in both eyes, 60% without previous ON.Interestingly, after 5 years of follow-up, 50% of patients treated with fingolimod increase the RNFL versus 10% of DMF, which it could mean less axonal damage in the FTY group, therefore OCT could be used as a biomarker to follow the treatment response.
  • ||||||||||  dimethyl fumarate / Generic mfg.
    [VIRTUAL] Systematic Evaluation and modeling of Dimethy Fumarate induced lymphopenia in MS cohort () -  Mar 6, 2021 - Abstract #ACTRIMSForum2021ACTRIMS_Forum_265;    
    In our cohort, at baseline most of patients present a reduction of RNFL thickness in both eyes, 60% without previous ON.Interestingly, after 5 years of follow-up, 50% of patients treated with fingolimod increase the RNFL versus 10% of DMF, which it could mean less axonal damage in the FTY group, therefore OCT could be used as a biomarker to follow the treatment response. Our study aims to identify factors associated with DMF induced lymphopenia, evaluate risk factors for patients and build a prediction model to provide more information for doctors to estimate patients’ benefits/risks for MS patients.
  • ||||||||||  Mavenclad (cladribine) / EMD Serono, Lemtrada (alemtuzumab) / Sanofi
    [VIRTUAL] DiseaseModifying Therapies for the Treatment of RelapsingRemitting Multiple Sclerosis: A Comparison of Their Efficacy for Reducing Relapse Rate () -  Mar 6, 2021 - Abstract #ACTRIMSForum2021ACTRIMS_Forum_225;    
    Although treatment responses varied, as well as comparators, the evaluated injectable, infused, and oral DMTs all provided a significant clinical benefit for relapse rate reduction. Innovations in the targeting/sequential monotherapy/escalation therapy/combination therapies towards the personalization of RRMS treatment will likely improve further the outcomes of patients with RRMS; future research in this regard is warranted in clinical trial and real-world settings.
  • ||||||||||  dimethyl fumarate / Generic mfg.
    [VIRTUAL] Modulation of Retinal Atrophy With Dimethyl Fumarate in Multiple Sclerosis () -  Mar 6, 2021 - Abstract #ACTRIMSForum2021ACTRIMS_Forum_206;    
    Our findings expand upon prior work and suggest a potential role for OCT-derived measures in assessing DMT potencies based upon retinal neuroprotection in MS clinical trials. Further analyses are necessary to investigate and compare changes in retinal atrophy rate during and after therapeutic DMT optimization.
  • ||||||||||  dimethyl fumarate / Generic mfg.
    Journal:  NRF2 mediates γ-globin gene regulation through epigenetic modifications in a β-YAC transgenic mouse model. (Pubmed Central) -  Mar 3, 2021   
    Although new treatments were recently approved by the FDA, only one drug Hydroxyurea induces fetal hemoglobin expression to inhibit sickle hemoglobin polymerization in red blood cells...Furthermore, an NRF2/TET3 interaction regulates γ-globin gene DNA methylation. These findings provide potential new molecular targets for small molecule drug developed for treating sickle cell disease.
  • ||||||||||  dimethyl fumarate / Generic mfg.
    Journal:  NRF2 and PPAR-γ Pathways in Oligodendrocyte Progenitors: Focus on ROS Protection, Mitochondrial Biogenesis and Promotion of Cell Differentiation. (Pubmed Central) -  Feb 26, 2021   
    We used dimethyl-fumarate (DMF) and pioglitazone (pio) as agents activating NRF2 and PPAR-γ, respectively, and two synthetic hybrids acting differently on the NRF2/ARE pathway...Finally, DMF, pio and compound 1 protected from tumor necrosis factor-alpha (TNF-α) insult, with pio showing faster kinetics of action and compound 1 a higher activity than DMF. In conclusion, NRF2 and PPAR-γ by inducing partially overlapping pathways accomplish complementary functions aimed at the preservation of mitochondrial function, the defense against oxidative stress and the promotion of OP differentiation.
  • ||||||||||  Lemtrada (alemtuzumab) / Sanofi
    Clinical, Review, Journal:  Differential Effects of MS Therapeutics on B Cells-Implications for Their Use and Failure in AQP4-Positive NMOSD Patients. (Pubmed Central) -  Feb 23, 2021   
    While lately approved disease-modifying drugs like ocrelizumab deplete B cells directly, most MS medications were not primarily designed to target B cells...In contrast, drugs such as natalizumab and interferon-β, which lead to activation and accumulation of B cells in the peripheral blood, lack efficacy or even induce catastrophic disease activity in NMOSD. Hence, we conclude that the differential effect of MS drugs on B cells is one potential parameter determining the therapeutic efficacy or failure in antibody-dependent diseases like seropositive NMOSD.
  • ||||||||||  dimethyl fumarate / Generic mfg., sirolimus / Generic mfg.
    Biomarker, Journal:  Immunometabolism at the cornerstone of inflammaging, immunosenescence, and autoimmunity in COVID-19. (Pubmed Central) -  Feb 23, 2021   
    Targeting this T-cell dysfunction opens the field for new therapeutic strategies to prevent severe COVID-19. Immunometabolism-mediated approaches such as rapamycin, metformin and dimethyl fumarate, may optimize COVID-19 treatment of the elderly and patients at risk for severe disease.
  • ||||||||||  Lemtrada (alemtuzumab) / Sanofi
    FDA event, Review, Journal:  Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System. (Pubmed Central) -  Feb 20, 2021   
    Furthermore, we point to a possible common molecular effect of these drugs, namely a key role for NFκB signaling, causing a switch from pro-inflammatory microglia and astrocytes to anti-inflammatory phenotypes of these CNS cell types that recently emerged as central players in MS pathogenesis. This notion argues for the need to further explore the molecular mechanisms underlying MS drug action.
  • ||||||||||  dimethyl fumarate / Generic mfg.
    Clinical, Journal:  SARS-CoV-2/COVID-19 in multiple sclerosis patients receiving disease-modifying therapy. (Pubmed Central) -  Feb 18, 2021   
    Two patients were treated with dimethyl fumarate, one with Interferon β1b and one with glatiramer acetate...All patients had symptoms of COVID-19 from the nervous system, the most frequent being headache, which occurred in all patients. The aim of this article is to present a case series of four patients with MS and COVID-19, and to discuss the available literature on COVID-19 in patients with MS, with particular consideration of the impact of DMT.
  • ||||||||||  dimethyl fumarate / Generic mfg.
    Clinical, Journal:  JCPyV NCCR analysis in PML patients with different risk factors: exploring common rearrangements as essential changes for neuropathogenesis. (Pubmed Central) -  Feb 13, 2021   
    The aim of this article is to present a case series of four patients with MS and COVID-19, and to discuss the available literature on COVID-19 in patients with MS, with particular consideration of the impact of DMT. The comparison of HIV-positive and HIV-negative MS patients with PML, allowed us to evidence the presence of a common pattern of JCPyV NCCR rearrangement, characterized by the deletion of the D-block, which could be one of the initial rearrangements of JCPyV NCCR needed for the development of PML.
  • ||||||||||  dimethyl fumarate / Generic mfg.
    Journal:  Prevention of Autoimmune Diabetes in NOD Mice by Dimethyl Fumarate. (Pubmed Central) -  Feb 13, 2021   
    The serum IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-12p70, IFN-γ, TNF-α, MCP-1 and CXCL16 levels in the DMF-treated group were lower than in the control group. In conclusion, DMF may protect islet cells and reduce the incidence of autoimmune diabetes in NOD mice by attenuating insulitis and proinflammatory cytokine production.
  • ||||||||||  Enrollment change:  RECOVERY: Randomised Evaluation of COVID-19 Therapy (clinicaltrials.gov) -  Feb 10, 2021   
    P2/3,  N=40000, Recruiting, 
    In conclusion, DMF may protect islet cells and reduce the incidence of autoimmune diabetes in NOD mice by attenuating insulitis and proinflammatory cytokine production. N=20000 --> 40000
  • ||||||||||  dimethyl fumarate / Generic mfg.
    Preclinical, Journal:  Neuroprotective Properties of Dimethyl Fumarate Measured by Optical Coherence Tomography in Non-inflammatory Animal Models. (Pubmed Central) -  Feb 2, 2021   
    While no protective effects were observed in optic nerve crush, in the light-induced retinal degeneration model DMF treatment significantly reduced retinal degeneration. In these mice, GSH levels in the retina and surrounding choroid were increased and histological investigations revealed less microglial activation in the outer retinal layers, suggesting both antioxidant and anti-inflammatory effects.
  • ||||||||||  dimethyl fumarate / Generic mfg.
    Clinical, Journal:  The expression analyses of RMRP, DDX5, and RORC in RRMS patients treated with different drugs versus naïve patients and healthy controls. (Pubmed Central) -  Jan 30, 2021   
    This study investigated the expression levels of RORC, DDX5, and RMRP in treatment-naïve relapsing-remitting multiple sclerosis (RRMS) patients, healthy controls, and RRMS patients treated with IFNβ-1α or fingolimod, or dimethyl fumarate (DMF), or glatiramer acetate (GA)...Our analyses have highlighted the high diagnostic value of RORC, DDX5, and RMRP in treatment-naïve RRMS patients. Furthermore, RMRP has demonstrated moderate positive correlations with the expression of DDX5 and RORC in treated RRMS patients.
  • ||||||||||  Tysabri (natalizumab) / Biogen, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    Clinical, Journal:  Effect of switching from natalizumab to moderate- vs high-efficacy DMT in clinical practice. (Pubmed Central) -  Jan 30, 2021   
    Of the patients included in the study, 48.6% switched to Mod DMT (dimethyl fumarate, n = 130; fingolimod, n = 140) vs 23.4% who switched to HET (ocrelizumab, n = 106; rituximab, n = 17; alemtuzumab, n = 7)...By 24 months post-NTZ, there was no difference in the annualized relapse rate (OR = 1.44, 95% CI [0.69-1.59], p = 0.334) or time to first clinical relapse (HR = 2.12, 95% CI [0.87-5.17], p = 0.090), although switchers to Mod DMT had higher gadolinium-enhancing (GdE) lesions (OR = 3.62, 95% CI [1.56-5.21], p = 0.005), earlier time to first GdE lesion (HR = 6.67, 95% CI [2.06-9.16], p = 0.002), lower proportion with the absence of disease activity (OR = 0.41, 95% CI [0.21-0.71], p = 0.004), and higher risk of disability progression on T25FW (OR = 1.83, 95% CI [1.06-3.02], p = 0.043) and 9-HPT (OR = 1.81, 95% CI [1.05-3.56], p = 0.044). Patients switching from NTZ to Mod DMT vs HET were at relatively increased risk of disease activity within the first 6 months of NTZ withdrawal that was sustained at 24 months, yielding greater disability progression.
  • ||||||||||  dimethyl fumarate / Generic mfg.
    Journal:  Design, synthesis and identification of novel, orally bioavailable non-covalent Nrf2 activators. (Pubmed Central) -  Jan 29, 2021   
    Covalent Keap1 inhibitors such as dimethyl fumarate (DMF) and RTA-408 are either on the market or in late stage clinical trials which implies potential benefit of Nrf2 activation...A representative analog shows excellent oral PK and good Nrf2-dependent gene inductions in kidney. These results provide a peripheral in vivo tool compound to validate the biology of non-covalent activation of Nrf2.
  • ||||||||||  dimethyl fumarate / Generic mfg.
    Clinical, Journal:  Clinical predictors of Dimethyl Fumarate response in multiple sclerosis: a real life multicentre study. (Pubmed Central) -  Jan 21, 2021   
    We confirm that DMF shows a good efficacy in both naïve patients and patients switching from other first-line DMTs, especially in patients with early onset of disease. Higher baseline EDSS was a risk factor for discontinuing DMF therapy, while shorter disease duration was protective for both EDSS progression and NEDA-3 status maintenance.
  • ||||||||||  dimethyl fumarate / Generic mfg.
    Preclinical, Journal:  Dimethyl fumarate protects thioacetamide-induced liver damage in rats: Studies on Nrf2, NLRP3, and NF-κB. (Pubmed Central) -  Jan 9, 2021   
    DMF treatment significantly ameliorated TAA-induced hepatic stellate cell activation, increase in inflammatory cascade markers (NACHT, LRR, and PYD domains-containing protein 3; NLRP3, apoptosis-associated speck like protein containing a caspase recruitment domain; ASC, caspase-1, nuclear factor-kappa B; NF-κB, interleukin-6), fibrogenic makers (α-smooth muscle actin; ɑ-SMA, transforming growth factor; TGF-β1, fibronectin, collagen 1) and antioxidant markers (nuclear factor (erythroid-derived 2)-like factor 2; Nrf2, superoxide dismutase-1; SOD-1, catalase). The present findings concluded that DMF protects against TAA-induced hepatic damage mediated through the downregulation of inflammatory cascades and upregulation of antioxidant status.
  • ||||||||||  dimethyl fumarate / Generic mfg.
    Biomarker, Journal:  Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease. (Pubmed Central) -  Jan 6, 2021   
    It is clear that NRF2 and its target genes can be readily assayed from PBMCs in multiple disease contexts and may track with disease progression. Further work needs to be undertaken to evaluate its stability but should be considered as an exploratory marker in clinical trials targeting NRF2 activation.