scholarly journals Ozanimod to Treat Relapsing Forms of Multiple Sclerosis: A Comprehensive Review of Disease, Drug Efficacy and Side Effects

2020 ◽  
Vol 12 (3) ◽  
pp. 89-108
Author(s):  
Grace Lassiter ◽  
Carlie Melancon ◽  
Tyler Rooney ◽  
Anne-Marie Murat ◽  
Jessica S. Kaye ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Drug Efficacy ◽  
Receptor Modulator ◽  
Increased Risk ◽  
Relapsing Remitting ◽  
The Us ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System ◽  
Us Fda ◽  
Reversible Encephalopathy

Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing–remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators.

FTY720 on the way from the base camp to the summit of the mountain: relevance for remyelination

2012 ◽  
Vol 18 (3) ◽  
pp. 258-263 ◽  
Author(s):  
M Kipp ◽  
S Amor
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Oral Disease ◽  
S1p Receptors ◽  
Receptor Modulator ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System

FTY720 (fingolimod; Gilenya®), a sphingosine 1-phosphate (S1P) receptor modulator, is the first oral disease-modifying therapy to be approved for the treatment of relapsing–remitting multiple sclerosis. FTY720 is rapidly converted in vivo to the active S-fingolimod-phosphate, which binds to S1P receptors. This action inhibits egress of lymphocytes from the lymph nodes, preventing entry into the blood and thus infiltration into the central nervous system. More recent studies, however, convincingly show that FTY720 crosses the blood–brain barrier, where it is thought to act on S1P receptors on cells within the central nervous system, such as astrocytes, oligodendrocytes or microglia. Here we discuss the evidence showing that FTY720 also plays a role in remyelination and repair within the brain. While the mechanisms of action still require firm elucidation, it is clear that FTY720 could also be reparative, extending its therapeutic potential for multiple sclerosis.

scholarly journals Does Siponimod Exert Direct Effects in the Central Nervous System?

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1771 ◽  
Author(s):  
Markus Kipp
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Direct Interaction ◽  
Active Role ◽  
Progressive Multiple Sclerosis ◽  
Receptor Subtypes ◽  
Receptor Modulator ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System

The modulation of the sphingosine 1-phosphate receptor is an approved treatment for relapsing multiple sclerosis because of its anti-inflammatory effect of retaining lymphocytes in lymph nodes. Different sphingosine 1-phosphate receptor subtypes are expressed in the brain and spinal cord, and their pharmacological effects may improve disease development and neuropathology. Siponimod (BAF312) is a novel sphingosine 1-phosphate receptor modulator that has recently been approved for the treatment of active secondary progressive multiple sclerosis (MS). In this review article, we summarize recent evidence suggesting that the active role of siponimod in patients with progressive MS may be due to direct interaction with central nervous system cells. Additionally, we tried to summarize our current understanding of the function of siponimod and discuss the effects observed in the case of MS.

The US FDA-Approved Drug Dimethyl Fumarate, an Nrf2 Activator, for Treating Multiple Sclerosis: The Mechanisms of Action Revisited

2021 ◽  
Vol 11 ◽  
Author(s):  
Editorial Office ROS
Keyword(s):  
Multiple Sclerosis ◽  
Immune Modulation ◽  
Aerobic Glycolysis ◽  
Dimethyl Fumarate ◽  
Relapsing Remitting ◽  
The Us ◽  
Us Fda ◽  
Nrf2 Activator ◽  
Species Production ◽  
Relapsing Remitting Multiple Sclerosis

Dimethyl fumarate, a potent Nrf2 activator and antioxidant-inducing compound, has been approved by the US Food and Drug Administration (FDA) as a first-line drug for treating relapsing forms of multiple sclerosis (MS). Two latest studies published in Nat Commun demonstrated that the efficacy of the drug in treating MS may be associated with increased reactive oxygen species production instead. REFERENCES Rothstein JD. Edaravone: a new drug approved for ALS. Cell 2017; 171(4):725. doi: https://dx.doi.org/10.1016/j.cell.2017.10.011. Ashrafian H, Czibik G, Bellahcene M, Aksentijevic D, Smith AC, Mitchell SJ, et al. Fumarate is cardioprotective via activation of the Nrf2 antioxidant pathway. Cell Metab 2012; 15(3):361–71. doi: https://dx.doi.org/10.1016/j.cmet.2012.01.017. Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 2012; 367(12):1098–107. doi: https://dx.doi.org/10.1056/NEJMoa1114287. Schulze-Topphoff U, Varrin-Doyer M, Pekarek K, Spencer CM, Shetty A, Sagan SA, et al. Dimethyl fumarate treatment induces adaptive and innate immune modulation independent of Nrf2. Proc Natl Acad Sci USA 2016; 113(17):4777–82. doi: https://dx.doi.org/10.1073/pnas.1603907113. Kornberg MD, Bhargava P, Kim PM, Putluri V, Snowman AM, Putluri N, et al. Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity. Science 2018; 360(6387):449–53. doi: https://dx.doi.org/10.1126/science.aan4665. Carlstrom KE, Ewing E, Granqvist M, Gyllenberg A, Aeinehband S, Enoksson SL, et al. Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis associates with ROS pathway in monocytes. Nat Commun 2019; 10(1):3081. doi: https://dx.doi.org/10.1038/s41467-019-11139-3. Luckel C, Picard F, Raifer H, Campos Carrascosa L, Guralnik A, Zhang Y, et al. IL-17+ CD8+ T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis. Nat Commun 2019; 10(1):5722. doi: https://dx.doi.org/10.1038/s41467-019-13731-z.

scholarly journals HIV infection and multiple sclerosis: a case with unexpected “no evidence of disease activity” status

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199957
Author(s):  
Fernando Labella ◽  
Fernando Acebrón ◽  
María del Carmen Blanco-Valero ◽  
Alba Rodrígez-Martín ◽  
Ángela Monterde Ortega ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Hiv Infection ◽  
Disease Activity ◽  
Demyelinating Disease ◽  
Clinical Course ◽  
Disease Modifying Drugs ◽  
Immunodeficiency Virus ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Disease Modifying

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system whose etiology remains unclear. It has been suggested that MS can be triggered by certain viruses; however, human immunodeficiency virus (HIV) infection is associated with reduced incidence of MS. We present the case of a young patient diagnosed with active relapsing-remitting MS whose clinical course substantially improved following HIV infection and treatment. The patient achieved no evidence of disease activity status without any disease-modifying drugs. Both HIV-induced immunosuppression and antiretroviral therapy may have attenuated the clinical course in this patient.

scholarly journals Evaluation the FLAIR Sensitivity and DWI Post-inject in Comparison with Delayed Enhancement T1w for Better Detection of Active MS Lesions

2018 ◽  
Author(s):  
M Hoseinipourasl ◽  
M Zandkarimi ◽  
J Abdolmohammadi ◽  
K Sharifi ◽  
S Miraki
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Factors ◽  
Vision Loss ◽  
Blurred Vision ◽  
Secondary Progressive ◽  
Signal Suppression ◽  
Relapsing Remitting ◽  
Loss Of Balance ◽  
The Central Nervous System ◽  
With Memory

Background: Multiple sclerosis (MS) is a chronic, typically progressive and most common autoimmune disease which damaged the central nervous system. According to the reports in 2008, this disorder has affected 2 and 2.5 million people globally. While the reason is not clear, proposed causes for this include immunologic, environmental, infectious and genetic factors, and sexuality. MS can cause many symptoms, including blurred vision, loss of balance, poor coordination, slurred speech, tremors, numbness, extreme fatigue, problems with memory and concentration, paralysis, blindness, and more. There are four distinguished illness fields in MS: relapsing-remitting MS (RRMS), primary–progressive MS (PPMS), secondary–progressive MS (SPMS), and progressive–relapsing. MRI is a great tool to identify the asymptomatic distribution of lesions in space and time.Materials and Methods: 32 patients with MS plaques were evaluated by FLAIR and DWI pre- and post-Gadolinium injection compared with 15minutes delay T1w SE.Results: FLAIR post-inject had significantly better detection of the number and signal intensity of active MS lesions. DWI and ADC images detected active plaques different from non-active lesions without contrast.Conclusion: The result of this study showed that FLAIR post-inject had the highest sensitivity in detection of active MS lesions due to the CSF signal suppression in FLAIR, thus offering enough TR time recovery in active enhanced plaques.

scholarly journals COVID-19 Vaccination Reactogenicity in Persons With Multiple Sclerosis

2021 ◽  
Vol 9 (1) ◽  
pp. e1104
Author(s):  
Farren Basil Shaw Briggs ◽  
Farrah J. Mateen ◽  
Hollie Schmidt ◽  
Keisha M. Currie ◽  
Heather M. Siefers ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Injection Site ◽  
Safety Information ◽  
Vaccine Dose ◽  
Research Network ◽  
Severe Reaction ◽  
Cross Sectional ◽  
Convenience Sample ◽  
Receptor Modulator ◽  
Sphingosine 1 Phosphate

Background and ObjectivesThere are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis–specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS.MethodsBetween 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes. Multivariable models characterized associations between clinical factors and reactogenicity.ResultsIn 719 PwMS, 64% reported experiencing a reaction after their first vaccination shot, and 17% reported a severe reaction. The most common reactions were pain at injection site (54%), fatigue (34%), headache (28%), and malaise (21%). Younger age, being female, prior SARS-CoV-2 infection, and receiving the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vs BNT162b2 (Pfizer-BioNTech) vaccine were associated with experiencing a reaction after the first vaccine dose. Similar relationships were observed for a severe reaction, including higher odds of reactions among PwMS with more physical impairment and lower odds of reactions for PwMS on an alpha4-integrin blocker or sphingosine-1-phosphate receptor modulator. In 442 PwMS who received their second vaccination shot, 74% reported experiencing a reaction, whereas 22% reported a severe reaction. Reaction profiles after the second shot were similar to those reported after the first shot. Younger PwMS and those who received the mRNA-1273 (Moderna) vs BNT162b2 vaccine reported higher reactogenicity after the second shot, whereas those on a sphingosine-1-phosphate receptor modulator or fumarate were significantly less likely to report a reaction.DiscussionSARS-CoV-2 vaccine reactogenicity profiles and the associated factors in this convenience sample of PwMS appear similar to those reported in the general population. PwMS on specific DMTs were less likely to report vaccine reactions. Overall, the short-term vaccine reactions experienced in the study population were mostly self-limiting, including pain at the injection site, fatigue, headache, and fever.

Expression of chemokine receptors in the different clinical forms of multiple sclerosis

2002 ◽  
Vol 8 (5) ◽  
pp. 390-395 ◽  
Author(s):  
E M Martínez-Cáceres ◽  
C Espejo ◽  
L Brieva ◽  
I Pericot ◽  
M Tintoré ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Chemokine Receptors ◽  
Surface Expression ◽  
Receptor Expression ◽  
Membrane Expression ◽  
System A ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Expression Characteristic ◽  
Peripheral Leukocytes

Chemokines and their receptors are important in the trafficking of peripheral leukocytes into the central nervous system, a major event in the pathogenesis of multiple sclerosis (MS). Evidence based on clinical, pathological and magnetic resonance imaging grounds supports some divergence between forms of MS with relapses [relapsing-remitting (RR) and secondary progressive (SP)] and the primary progressive (PP) form. To elucidate whether different pathogenic mechanisms are involved in PPMS, we compared membrane expression of a group of CC and CXC chemokine receptors (CCR1, CCR5, CXCR3, CXCR4) in peripheral blood of 68 MS patients (25 PPMS, 23 SPMS and 20 RRMS) and 26 healthy controls. We found a significant increase in surface expression of CCR5 in CD4+, CD8+, CD19+ and CD14+ cells as well as an increased percentage of CXCR3 and CXCR4 in CD14+ cells in MS patients compared to controls. Increased levels of CXCL10 (IP-10) and CCL5 (RANTES) in cerebrospinal fluid were also observed in a subgroup of MS patients. These results support that chemokines and their receptors are involved in the pathogenesis of MS. However, a pattern of chemokine-chemokine receptor expression characteristic of each clinical form of the disease failed to be observed.

Delayed fingolimod-associated asystole

2011 ◽  
Vol 17 (11) ◽  
pp. 1387-1389 ◽  
Author(s):  
Patricio S Espinosa ◽  
Joseph R Berger
Keyword(s):  
Multiple Sclerosis ◽  
Lymph Nodes ◽  
Disability Progression ◽  
Receptor Modulator ◽  
Sphingosine 1 Phosphate

Oral fingolimod (Gilenya) is a sphingosine-1-phosphate-receptor modulator that prevents the egress of lymphocytes from lymph nodes. Fingolimod reduces relapses and delays disability progression in patients with relapsing forms of multiple sclerosis (MS). We report a patient with MS who developed asystole and sustained bradycardia 21 hours after the first dose of fingolimod.

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