Neurotherapeutics in multiple sclerosis: Novel agents and emerging treatment strategies

DeAngelis, Tracy M.; Lublin, Fred

doi:10.1002/msj.20030

Cited by 23 publications

(20 citation statements)

References 46 publications

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“…New oral immunomodulatory therapies including dimethyl fumarate, teriflunomide, and alemtuzumab are pending FDA approval for the treatment of RRMS and will soon be new therapies to consider for the treatment of CIS. 110 Researchers are also trying to identify effective and safe neuroprotective agents that are anticipated to offer new avenues for prevention and repair in the future management of CIS and MS. It is likely that such agents will be used in combination with therapies that prevent MS relapses.…”

Section: Disease-modifying Therapy In Cis-transition To Outpatient Mamentioning

confidence: 99%

Updates on Clinically Isolated Syndrome and Diagnostic Criteria for Multiple Sclerosis

Marcus

Waubant

2012

The Neurohospitalist

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Clinically isolated syndrome (CIS) is a central nervous system demyelinating event isolated in time that is compatible with the possible future development of multiple sclerosis (MS). Early risk stratification for conversion to MS helps with treatment decisions. Magnetic resonance imaging (MRI) is currently the most useful tool to evaluate risk. Cerebrospinal fluid studies and evoked potentials may also be used to assess the likelihood of MS. Four clinical trials evaluating the benefits of either interferon b (IFN-b) or glatiramer acetate (GA) within the first 3 months after a high-risk CIS demonstrate decreased rates of conversion to clinically definite MS (CDMS) and a lesser degree of MRI progression with early treatment. In the 3-, 5-, and 10-year extension studies of 2 formulations of IFN-b, the decreased conversion rate to CDMS remained meaningful when comparing early treatment of CIS to treatment delayed by a median of 2 to 3 years. Diagnostic criteria have been developed based on the clinical and MRI follow-up of large cohorts with CIS and provide guidance on how to utilize clinical activity in combination with radiographic information to diagnose MS. The most recent 2010 McDonald criteria simplify requirements for dissemination in time and space and allow for diagnosis of MS from a baseline brain MRI if there are both silent gadolinium-enhancing lesions and nonenhancing lesions on the same imaging study. The diagnostic criteria for MS require special consideration in children at risk for acute disseminated encephalomyelitis (ADEM), in older adults who may have small vessel ischemic disease, and in ethnic groups that more commonly develop neuromyelitis optica (NMO).

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Section: Disease-modifying Therapy In Cis-transition To Outpatient Mamentioning

confidence: 99%

Updates on Clinically Isolated Syndrome and Diagnostic Criteria for Multiple Sclerosis

Marcus

Waubant

2012

The Neurohospitalist

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“…However, these are only partly effective and may not have a significant effect on overall disease progression (DeAngelis and Lublin, 2008b). New therapies are being developed, including novel immunomodulatory agents that are aimed at inhibiting specific aspects of the immune system, thereby reducing the autoimmune attack on oligodendrocytes and myelin.…”

Section: Promoting Remyelination Is An Important Objective For Futurementioning

confidence: 99%

“…For example, alemtuzumab is an antibody that targets lymphocytes and monocytes and has generated promising results in clinical trials (Coles et al, 2008). These new therapies are reviewed elsewhere (DeAngelis and Lublin, 2008a;DeAngelis and Lublin, 2008b;Kieseier et al, 2007).…”

Section: Promoting Remyelination Is An Important Objective For Futurementioning

confidence: 99%

Zebrafish myelination: a transparent model for remyelination?

Buckley

Goldsmith²,

Franklin³

2008

Disease Models &Amp; Mechanisms

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There is currently an unmet need for a therapy that promotes the regenerative process of remyelination in central nervous system diseases, notably multiple sclerosis (MS). A high-throughput model is, therefore, required to screen potential therapeutic drugs and to refine genomic and proteomic data from MS lesions. Here, we review the value of the zebrafish (Danio rerio) larva as a model of the developmental process of myelination, describing the powerful applications of zebrafish for genetic manipulation and genetic screens, as well as some of the exciting imaging capabilities of this model. Finally, we discuss how a model of zebrafish myelination can be used as a high-throughput screening model to predict the effect of compounds on remyelination. We conclude that zebrafish provide a highly versatile myelination model. As more complex transgenic zebrafish lines are developed, it might soon be possible to visualise myelination, or even remyelination, in real time. However, experimental outputs must be designed carefully for such visual and temporal techniques.

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“…Although the exact aetiology of MS remains unclear, it is likely caused by dysregulation of the immune system leading to injury of the nervous system which is triggered through a multifactorial pathway of genetic predisposition and environmental triggers (e.g. geographic latitude, vitamin D deficiency, viruses, and smoking) [1, 2]. With an age onset of 20–40, overall incidence rate of MS is 3.6 cases per 100,000 person-years in women and 2.0 in men [3].…”

Section: Introductionmentioning

confidence: 99%

Original research A meta-analysis on the efficacy and tolerability of natalizumab in relapsing multiple sclerosis

Nikfar¹,

Rahimi²,

Rezaie³

et al. 2010

aoms

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IntroductionNatalizumab is a new humanized monoclonal antibody used in multiple sclerosis (MS). The aim of this meta-analysis was to evaluate the efficacy and tolerability of this drug in relapsing MS. PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies that investigated the efficacy and/or tolerability of natalizumab in MS. Data were collected from 1966 to 2008 (up to October).Material and methodsThe search terms were: “multiple sclerosis” or “MS” and “natalizumab”. “Mean change in Expanded Disability Status Scale (EDSS)”, “number of patients with at least one relapse”, and “number of patients with at least one new gadolinium (Gd)-enhancing lesion” were the key outcomes of interest for assessment of efficacy. “Any adverse events”, “serious adverse events”, “death”, and “withdrawal because of adverse events” were the key outcomes for tolerability. Among existing trials, four randomized placebo controlled clinical trials met our criteria and were included.ResultsPooled relative risk for at least one relapse in four trials including all doses was 0.7, with a non-significant RR (95% CI: 0.42–1.17, p = 0. 17). Summary RR for at least one relapse in two trials in which doses of 3 mg/kg or 6 mg/kg or 300 mg every 4 weeks were administered gave a value of 0.5 asa significant RR (95% CI: 0.42–0.61, p < 0.0001). The summary RR for at least one new Gd-enhancing lesion was 0.22, a non-significant RR (95% CI: 0.05–1.01, p = 0.051). Three deaths were reported in the natalizumab group. Comparing adverse events between natalizumab and placebo yielded a non-significant RR of 0.99 (95% CI: 0.96–1.01, p = 0.34) for any adverse events (n = 3), and a significant RR of 0.39 (95% CI: 0.29–0.52, p < 0.0001) for serious adverse events (n = 2). The summary RR for withdrawal due to adverse events by natalizumab vs. placebo therapy between two trials was 1.43, a non-significant RR (95% CI: 0.68–3.02, p = 0.35).ConclusionsIt seems that using 3 or 6 mg/kg every 4 weeks is the best method of administration of natalizumab for preventing relapse and occurrence of new Gd-enhancing lesions. The current data on the efficacy and safety of natalizumab are insufficient to reach a convincing conclusion and thus further clinical trials are still needed.

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Neurotherapeutics in multiple sclerosis: Novel agents and emerging treatment strategies

Cited by 23 publications

References 46 publications

Updates on Clinically Isolated Syndrome and Diagnostic Criteria for Multiple Sclerosis

Updates on Clinically Isolated Syndrome and Diagnostic Criteria for Multiple Sclerosis

Zebrafish myelination: a transparent model for remyelination?

Original research A meta-analysis on the efficacy and tolerability of natalizumab in relapsing multiple sclerosis

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