Advances in the Treatment of Multiple Sclerosis

Goldschmidt, Carolyn; McGinley, Marisa

doi:10.1016/j.ncl.2020.09.002

Cited by 42 publications

(37 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the cellular level, MS is characterized by pronounced demyelination, axonal degeneration, neuronal inflammation, and glial activation. MS treatment includes three main strategies: treatment of relapse with anti-inflammatory drugs, symptomatic treatment, and the use of drugs that change the disease course (disease-modifying therapies; DMTs) ( DeLuca et al, 2020 ; Goldschmidt and McGinley, 2021 ).…”

Section: Role Of Hif-1α In Neurodegenerative Diseasesmentioning

confidence: 99%

Hypoxia-Inducible Factor (HIF) in Ischemic Stroke and Neurodegenerative Disease

Митрошина

Savyuk

Ponimaskin

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Hypoxia is one of the most common pathological conditions, which can be induced by multiple events, including ischemic injury, trauma, inflammation, tumors, etc. The body’s adaptation to hypoxia is a highly important phenomenon in both health and disease. Most cellular responses to hypoxia are associated with a family of transcription factors called hypoxia-inducible factors (HIFs), which induce the expression of a wide range of genes that help cells adapt to a hypoxic environment. Basic mechanisms of adaptation to hypoxia, and particularly HIF functions, have being extensively studied over recent decades, leading to the 2019 Nobel Prize in Physiology or Medicine. Based on their pivotal physiological importance, HIFs are attracting increasing attention as a new potential target for treating a large number of hypoxia-associated diseases. Most of the experimental work related to HIFs has focused on roles in the liver and kidney. However, increasing evidence clearly demonstrates that HIF-based responses represent an universal adaptation mechanism in all tissue types, including the central nervous system (CNS). In the CNS, HIFs are critically involved in the regulation of neurogenesis, nerve cell differentiation, and neuronal apoptosis. In this mini-review, we provide an overview of the complex role of HIF-1 in the adaptation of neurons and glia cells to hypoxia, with a focus on its potential involvement into various neuronal pathologies and on its possible role as a novel therapeutic target.

show abstract

Section: Role Of Hif-1α In Neurodegenerative Diseasesmentioning

confidence: 99%

Hypoxia-Inducible Factor (HIF) in Ischemic Stroke and Neurodegenerative Disease

Митрошина

Savyuk

Ponimaskin

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…The choice of DMT is influenced by a variety of factors—mechanisms of action, efficacy, dosing schedules, routes of administration, tolerability, and safety—which differ by DMT [ 12 ]. Available DMTs for MS consist of injectable, oral, and infusion therapies across nine drug classes [ 13 ]. Injectables were the first DMTs approved in the 1990s and include the immune modulators interferon beta-1b and glatiramer acetate for treatment for RRMS.…”

Section: Introductionmentioning

confidence: 99%

“…In 2004, the first infusion therapeutic, natalizumab, was approved, and since then, other immune suppressant infusions such as alemtuzumab and ocrelizumab have been approved. The first oral DMT, fingolimod, was approved in 2010 and, as of April 2020, there were six additional approved oral treatments for MS, including cladribine, dimethyl fumarate, diroximel fumarate, ozanimod, teriflunomide, and siponimod [ 13 ]. Adherence and persistence to DMT regimens are of critical importance in achieving full efficacy; however, real-world studies of DMT treatment patterns in MS have reported suboptimal adherence rates [ 10 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Retrospective Claims Analysis of Treatment Patterns, Relapse, Utilization, and Cost Among Patients with Multiple Sclerosis Initiating Second-Line Disease-Modifying Therapy

Freeman

Kee

Tian

et al. 2021

Drugs - Real World Outcomes

View full text Add to dashboard Cite

Background Real-world studies of disease-modifying therapies (DMTs) in multiple sclerosis (MS) have reported suboptimal adherence. Objective We aimed to describe treatment patterns, relapses, healthcare resource utilization, and costs in MS patients experiencing their first observed DMT switch. Methods In this retrospective, claims database study, adult patients were selected if they had an MS diagnosis and DMT claim during the study period (1 January 2009-31 March 2019). Patients who switched to a new DMT between 1 January 2010 and 31 March 2018 were included. Adherence, persistence, relapses, and all-cause and MS-related healthcare utilization and costs were reported pre-and post-index. Results In total, 1554 MS patients were identified; the mean age was 46 years and most (74%) were female. The majority of patients switched from an injectable DMT (n = 1116; 71.8%), and patients generally switched to an oral DMT (n = 878; 57%). Among patients who switched DMTs, 46.0% (n = 715) were nonadherent, 42% (n = 645) were nonpersistent, and 21.5% (n = 334) relapsed in the 12 months post-switch. An increase in all-cause and MS-related healthcare costs was observed pre-to post-index for all patients. Cost drivers included outpatient visit costs and pharmacy prescriptions. Compared with patients who switched to an injectable DMT, those who switched to an oral DMT had significantly higher persistence and adherence. No significant difference was observed in post-index relapse or all-cause and MS-related total cost of care. Conclusion Low adherence and poor persistence remain following an initial DMT switch; however, patients who switched to oral DMTs had higher persistence and adherence. Plain Language SummaryMultiple sclerosis (MS) is a disabling disease that is treated with disease-modifying therapies (DMTs). Little is known about how patients with MS take their medication, how disease progression may change with treatment, or what the impact of switching to a new DMT is on the cost of care. In an analysis of commercially insured individuals, patients with MS were examined before and after switching to a new DMT. Results showed that the patients most often switched from an injectable medication to an oral DMT; however, a large proportion of patients did not take the prescription as directed by their physician. Additionally, a large proportion of patients did not stay on their new therapy. Nearly one-third of patients experienced an MS relapse after they switched to a new treatment, and healthcare costs increased following the treatment switch. A higher proportion of patients switching to an oral DMT took their medication as prescribed by their physicians, stayed on therapy, and incurred smaller increases in cost compared with patients switching to injectable medications. Despite such improvements, additional treatments are needed for patients with MS.

show abstract

“…The current therapeutic strategy is based on immunomodulatory drugs like interferon beta (IFN-β), glatiramer acetate, natalizumab, ngolimod, etc. [12,10]. The therapeutic e cacy of these compounds is limited by signi cant side effects and the high variability of individual drug response probably because of disease heterogeneity [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Piperine Improves Experimental Autoimmune Encephalomyelitis (EAE) in Lewis Rats Through its Neuroprotective, Anti-inflammatory, and Antioxidant Effects

et al. 2021

View full text Add to dashboard Cite

In ammation, demyelination, glial activation, and oxidative damage are the most pathological hallmarks of multiple sclerosis (MS). Piperine, a main bioactive alkaloid of black pepper, possesses antioxidant, anti-in ammatory and neuroprotective properties whose therapeutic potential has been less studied in the experimental autoimmune encephalomyelitis (EAE) models. In this study, the e ciency of peprine on progression of EAE model and myelin repair mechanisms was investigated. EAE was induced in female Lewis rats and piperine and its vehicle were daily administrated intraperitoneally from day 8 to 29 post immunization. We found that peperine alleviated neurological de cits and EAE disease progression. Luxol fast blue and H&E staining and immuno-staining of lumbar spinal cord cross sections con rmed that piperine signi cantly reduced the extent of demyelination, in ammation and immune cell in ltration and inhibited microglia and astrocyte activation. Gene expression analysis in lumbar spinal cord showed that piperine treatment decreased the level of pro-in ammatory cytokines (TNF-α, IL-1β) and iNOS and enhanced IL-10, Nrf-2, HO-1and MBP expressions. Piperine supplementation also enhanced the total antioxidant capacity (FRAP) and reduced the level of oxidative stress marker (MDA) in the CNS of EAE rats. Finally, we found that piperine has anti-apoptotic and neuroprotective effect in EAE through reducing caspase-3 (apoptosis marker) and enhancing BDNF and NeuN expressing cells. This study strongly indicates that piperine has a bene cial effect on the EAE progression and could be considered as a potential therapeutic target for MS treatment. Upcoming clinical trials will provide the deep understanding of piperine's role for the treatment of the MS.

show abstract

Advances in the Treatment of Multiple Sclerosis

Cited by 42 publications

References 48 publications

Hypoxia-Inducible Factor (HIF) in Ischemic Stroke and Neurodegenerative Disease

Hypoxia-Inducible Factor (HIF) in Ischemic Stroke and Neurodegenerative Disease

Retrospective Claims Analysis of Treatment Patterns, Relapse, Utilization, and Cost Among Patients with Multiple Sclerosis Initiating Second-Line Disease-Modifying Therapy

Piperine Improves Experimental Autoimmune Encephalomyelitis (EAE) in Lewis Rats Through its Neuroprotective, Anti-inflammatory, and Antioxidant Effects

Contact Info

Product

Resources

About