scholarly journals Charting a global research strategy for progressive MS—An international progressive MS Alliance proposal

2021 ◽  
pp. 135245852110597
Author(s):  
Alan J Thompson ◽  
William Carroll ◽  
Olga Ciccarelli ◽  
Giancarlo Comi ◽  
Anne Cross ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Biomarker Discovery ◽  
Steering Committee ◽  
Progressive Multiple Sclerosis ◽  
Research Strategy ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Secondary Progressive ◽  
Underlying Mechanisms ◽  
Global Research

Background: Progressive forms of multiple sclerosis (MS) affect more than 1 million individuals globally. Recent approvals of ocrelizumab for primary progressive MS and siponimod for active secondary progressive MS have opened the therapeutic door, though results from early trials of neuroprotective agents have been mixed. The recent introduction of the term ‘active’ secondary progressive MS into the therapeutic lexicon has introduced potential confusion to disease description and thereby clinical management. Objective: This paper reviews recent progress, highlights continued knowledge and proposes, on behalf of the International Progressive MS Alliance, a global research strategy for progressive MS. Methods: Literature searches of PubMed between 2015 and May, 2021 were conducted using the search terms “progressive multiple sclerosis”, “primary progressive multiple sclerosis”, “secondary progressive MS”. Proposed strategies were developed through a series of in-person and virtual meetings of the International Progressive MS Alliance Scientific Steering Committee. Results: Sustaining and accelerating progress will require greater understanding of underlying mechanisms, identification of potential therapeutic targets, biomarker discovery and validation, and conduct of clinical trials with improved trial design. Encouraging developments in symptomatic and rehabilitative interventions are starting to address ongoing challenges experienced by people with progressive MS. Conclusion: We need to manage these challenges and realise the opportunities in the context of a global research strategy, which will improve quality of life for people with progressive MS.

Mitoxantrone as a potential therapy for primary progressive multiple sclerosis

2004 ◽  
Vol 10 (3_suppl) ◽  
pp. S58-S61 ◽  
Author(s):  
Olaf Stüve ◽  
Mariko Kita ◽  
Daniel Pelletier ◽  
Robert J Fox ◽  
Jerome Stone ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Western Europe ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Pharmacological Properties ◽  
Phase 2 ◽  
Double Blind ◽  
Primary Progressive ◽  
Secondary Progressive ◽  
Phase 2 Trial

Mitoxantrone (Novantrone®) was the first drug approved in western Europe and North A merica for treatment of secondary progressive multiple sclerosis (SPMS) and progressive relapsing MS (PRMS). Pharmacological properties of mitoxantrone, its role in SPMS, the study rational and design of an ongoing multi-centre, double blind, randomized, placebo -controlled phase 2 trial will be outlined in this article.

Circulating microRNAs as biomarkers in progressive multiple sclerosis

2016 ◽  
Vol 23 (3) ◽  
pp. 403-412 ◽  
Author(s):  
Julia Vistbakka ◽  
Irina Elovaara ◽  
Terho Lehtimäki ◽  
Sanna Hagman
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Progressive Multiple Sclerosis ◽  
Body Fluids ◽  
Primary Progressive Multiple Sclerosis ◽  
Circulating Mirnas ◽  
Circulating Micrornas ◽  
Primary Progressive ◽  
Secondary Progressive ◽  
Exceptional Stability

Background: In multiple sclerosis (MS), microRNA (miRNA) dysregulation is mostly reported in different immune cells, but less information is available on circulating miRNAs that exert strong biomarker potential due to their exceptional stability in body fluids. Objective: The aim of this study was to profile expression of circulating miRNAs in primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS) and assess their association with neurological worsening. Methods: The expressions of 84 different miRNAs were profiled in serum of 83 subjects (62 MS and 21 controls) using miScript miRNA techniques. First, they were screened on 18 PPMS and 10 controls; thereafter, 10 most aberrantly expressed miRNAs were validated on a larger cohort. Results: In comparison with controls, upregulation of miR-191-5p was found in both progressive MS subtypes, while miR-376c-3p was overexpressed only in PPMS. Additionally, upregulation of miR-128-3p and miR-24-3p was detected in PPMS when compared to controls and SPMS. Progression index correlated with miR-128-3p in PPMS and miR-375 in SPMS. Conclusion: We detected overexpression of four miRNAs that have not been previously associated with progressive forms of MS. The increased expression of circulating miR-191-5p seems to be associated with progressive forms of MS, while miR-128-3p seems to be associated mostly with PPMS.

scholarly journals Greater loss of axons in primary progressive multiple sclerosis plaques compared to secondary progressive disease

Brain ◽  
2009 ◽  
Vol 132 (5) ◽  
pp. 1190-1199 ◽  
Author(s):  
E. C. Tallantyre ◽  
L. Bo ◽  
O. Al-Rawashdeh ◽  
T. Owens ◽  
C. H. Polman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Disease ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Secondary Progressive

The pathology of primary progressive multiple sclerosis

2002 ◽  
Vol 8 (2) ◽  
pp. 93-97 ◽  
Author(s):  
W Brück ◽  
C Lucchinetti ◽  
H Lassmann
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Current Knowledge ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Underlying Pathology ◽  
Clinical Subtype

The present review will focus on the current knowledge of the pathology of primary progressive multiple sclerosis lesions. Multiple sclerosis (MS) is an inflammatory demyelinating disease with a broad clinical variability. The main disease courses are relapsing-remitting, secondary progressive and primary progressive MS. Pathological studies examining the specific underlying pathology of a defined clinical subtype are rare. Here, we focus on the phatological characteristics of the MS lesions and summarize the current findings of the phatology of primary progressive MS with respect to inflammation, oligodendrocyte/myelin pathology, axon destruction and immunopathology of the lesions.

Primary progressive multiple sclerosis: cerebrospinal fluid considerations

2004 ◽  
Vol 10 (3_suppl) ◽  
pp. S31-S35
Author(s):  
Mark S Freedman
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
State Of The Art ◽  
Disease Process ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Secondary Progressive ◽  
Current State ◽  
Relapsing Remitting

Diagnosing the ‘primary progressive’ form of multiple sclerosis (PPMS) requires assurance that other conditions that might cause a chronic inflammatory neurodegenerative central nervous system (CNS) disease have been ruled out. Both imaging and pathological studies have shown that this form of MS tends to be less inflammatory compared with either the relapsing-remitting or secondary progressive types. There are therefore many conditions that cause a slowly progressive wasting of the C NS that might be confused with MS. The new MS diagnostic scheme has made the presence of ‘typical’ MS abnormalities in the cerebrospinal fluid (C SF) a mandatory first criterion, but there may well be individuals that still have PPMS even in the absence of a typical MS C SF. Here we explore what the C SF can tell about an individual’s disease process and outline the current state of the art in terms of C SF analysis. Used properly, the C SF can be very helpful in clarifying a diagnosis of PPMS.

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