scholarly journals Current advancements in promoting remyelination in multiple sclerosis

2018 ◽  
Vol 25 (1) ◽  
pp. 7-14 ◽  
Author(s):  
David Kremer ◽  
Rainer Akkermann ◽  
Patrick Küry ◽  
Ranjan Dutta
Keyword(s):  
Multiple Sclerosis ◽  
Precursor Cells ◽  
Resonance Imaging ◽  
Major Focus ◽  
Short Term ◽  
Myelin Repair ◽  
Relapsing Remitting ◽  
Oligodendrocyte Precursor ◽  
Magnetic Resonance Imaging Mri ◽  
Endogenous Process

Current multiple sclerosis (MS) therapies are effective in reducing relapse rate, short-term measures of disability, and magnetic resonance imaging (MRI) measures of inflammation in relapsing remitting MS (RRMS), whereas in progressive/degenerative disease phases these medications are of little or no benefit. Therefore, the development of new therapies aimed at reversing neurodegeneration is of great interest. Remyelination, which is usually a spontaneous endogenous process, is achieved when myelin-producing oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs). Even though these precursor cells are abundant in MS brains, their regeneration capacity is limited. Enhancing the generation of myelin-producing cells is therefore a major focus of MS research. Here we present an overview of the different advancements in the field of remyelination, including suitable animal models for testing remyelination therapies, approved medications with a proposed role in regeneration, myelin repair treatments under investigation in clinical trials, as well as future therapeutics aimed at facilitating myelin repair.

Does MRI lesion activity regress in secondary progressive multiple sclerosis?

2010 ◽  
Vol 16 (4) ◽  
pp. 434-442 ◽  
Author(s):  
Y. Zhao ◽  
AJ Petkau ◽  
A. Traboulsee ◽  
A. Riddehough ◽  
DKB Li
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Short Term ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri ◽  
Short Term Trend

Background: The rate of new contrast-enhancing lesions (CELs) on monthly magnetic resonance imaging (MRI) scans has been shown to decrease over a 9-month period in placebo-treated patients with relapsing—remitting (RR) multiple sclerosis (RRMS). Objective: We examined this phenomenon in placebo-treated secondary progressive MS (SPMS) patients. Methods: Patients were chosen from two clinical trials. Monthly scans were taken at screening, baseline and months 1—9 for Cohort-1 and months 1—6 for Cohort-2. We examined the monthly new CEL rates according to initial CEL level: 0, 1—3, >3 CELs at screening, and presence and absence of pre-study relapses. Results: Respectively, 59, 21 and 14 of the 94 Cohort-1 patients, and 36, 17 and 9 of the 62 Cohort-2 patients had 0, 1—3 and >3 initial CELs. For Cohort-1, the monthly new CEL rates did not change during follow-up, regardless of initial CEL level. For Cohort-2, the monthly rate was unchanged in the 0 initial CEL subgroup, but decreased 33% (95% confidence interval: 8%, 52%) from months 1—3 to months 4—6 in the other two subgroups. For the combined cohorts, a decreasing rate was observed in the 12 patients with >3 initial CELs and pre-study relapses. Conclusions: The short-term trend of new CEL activity in placebo-treated SPMS patients may vary across cohorts.

Can rate of brain atrophy in multiple sclerosis be explained by clinical and MRI characteristics?

2008 ◽  
Vol 15 (4) ◽  
pp. 465-471 ◽  
Author(s):  
T Korteweg ◽  
M Rovaris ◽  
V Neacsu ◽  
M Filippi ◽  
G Comi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Atrophy ◽  
Lesion Volume ◽  
Stepwise Multiple Linear Regression ◽  
Resonance Imaging ◽  
Short Term ◽  
Focal Lesions ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Mri Characteristics

Introduction Multiple sclerosis (MS) is characterized, besides focal lesions, by brain atrophy. The determinants of atrophy rates in individual patients are poorly understood. Aim This study investigated the predictive value of clinical and magnetic resonance imaging (MRI) factors, including short-term changes thereof, for concurrent and future atrophy evolution using Spearman’s rank correlations and stepwise multiple linear regression. Methods We retrospectively identified a group of 115 active, early relapsing-remitting (RR) patients relatively homogeneous in terms of disease course and MRI activity compared to a second group of 96 patients with broader spectrum of MS phenotypes and inactive scans. All patients had undergone three MRI investigations with interscan intervals of at least 12 and 24 months, respectively. Results In the RR patients, 23% of variance in concurrent atrophy rates (over the first interval) could be explained by the combination of baseline T2 lesion volume and change in EDSS score over the first interval, whereas only 6% in future atrophy rates (over the second interval) was explained. In the heterogeneous group, 20.2% of the variance in future atrophy rates could be explained, but slightly less in concurrent atrophy rates (16.2%). Conclusion We concluded that variance in brain atrophy rates can partially be explained by clinical and MRI measures of disease. Future atrophy rates in individual MS patients are difficult to predict even when including previous atrophy rates.

Modelling new enhancing MRI lesion counts in multiple sclerosis

2001 ◽  
Vol 7 (5) ◽  
pp. 298-304 ◽  
Author(s):  
M P Sormani ◽  
P Bruzzi ◽  
M Rovaris ◽  
F Barkhof ◽  
G Comi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Negative Binomial ◽  
Surrogate Marker ◽  
Parametric Models ◽  
Parametric Modelling ◽  
Resonance Imaging ◽  
Baseline Activity ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri

Magnetic resonance imaging (MRI) has been established as the most relevant paraclinical tool for diagnosing and monitoring multiple sclerosis (MS). In this context, counting the number of new enhancing lesions on monthly MRI scans is widely used as a surrogate marker of MS activity when evaluating the effect of treatments. In this study, we investigated whether parametric models based on mixed Poisson distributions (the Negative Binomial (NB) and the Poisson-Inverse Gaussian (P-IG) distributions) were able to provide adequate fitting of new enhancing lesion counts in MS. We found that the NB model gave good approximations in relapsing7remitting and secondary progressive MS patients not selected for baseline MRI activity, whereas the P-IG distribution modelled better new enhancing lesion counts in relapsing-remitting MS patients selected for baseline activity. This study shows that parametric modelling for MS new enhancing lesion counts is feasible. This approach should provide more targeted tools for the design and the analysis of MRI monitored clinical trials in MS.

MRI-based analysis of the natalizumab therapeutic window in multiple sclerosis

2012 ◽  
Vol 18 (9) ◽  
pp. 1337-1339 ◽  
Author(s):  
Luigi ME Grimaldi ◽  
Luca Prosperini ◽  
Gaetano Vitello ◽  
Giovanna Borriello ◽  
Federica Fubelli ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Therapeutic Window ◽  
Resonance Imaging ◽  
Therapy Discontinuation ◽  
Dosing Interval ◽  
Relapsing Remitting ◽  
Mri Scans ◽  
Magnetic Resonance Imaging Mri

The recommended natalizumab dosage is 300 mg every 4 weeks. We evaluated radiological activity at various times from the last natalizumab infusion by examining 386 magnetic resonance imaging (MRI) scans from 166 natalizumab-treated patients with relapsing–remitting MS. Of 113 scans performed >4 weeks after last natalizumab infusion, 26 were active (i.e. had ≥1 contrast-enhancing lesions). Risk of radiological activity increased by 1.34 fold for each week of delay with respect to the recommended 4-week dosing interval, compared with schedule-adherent patients ( p<0.0001). Our data suggest that an increased MRI activity ≥7 weeks from the last infusion of natalizumab should be considered in cases of therapy discontinuation.

Specific power calculations for magnetic resonance imaging (MRI) in monitoring active relapsing-remitting multiple sclerosis (MS): implications for phase II therapeutic trials

1997 ◽  
Vol 2 (6) ◽  
pp. 283-290 ◽  
Author(s):  
L Truyen ◽  
F Barkhof ◽  
M Tas ◽  
MAA Van Walderveen ◽  
STFM Frequin ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Median Number ◽  
Specific Power ◽  
Resonance Imaging ◽  
Power Calculations ◽  
Relapsing Remitting ◽  
Magnetic Resonance Imaging Mri ◽  
Trial Monitoring

Inhomogeneous patient samples have been used in previous studies to determine the power of magnetic resonance imaging (MRI) for trial monitoring in multiple sclerosis (MS). These power-calculations might not be applicable to the active relapsing-remitting patient who is preferably included in trials. In order to reevaluate the power alculations for MRI in the monitoring of treatment in strictly relapsing-remitting MS and to compare the power of different trial designs we studied 12 relapsing-remitting MS patients prospectively for a median period of II months using monthly clinical assessments and gadolinium-enhanced MRI. A median number of two clinical relapses/patient occurred of which a median of one was treated with steroids. A median of 1.59 new lesions/scan/patient was detected (range 0–8). The total number of new active lesions correlated significantly with study period relapses (SRCC=0.72, P=0.023). Computer simulations using the bootstrap technique yielded mostly lower power values for a parallel groups design than in previous studies except for short follow-periods in larger samples. In this sample the open cross-over design was found to be between 20 and 40% more powerful. Results of power-calculations are clearly sample dependent implying that for treatment trial monitoring using MRI in relapsing-remitting MS conservative sample size estimates are to be used. In an active patient group open cross-over trial designs could be a very powerful alternative to parallel groups design.

The distribution of the magnetic resonance imaging response to glatiramer acetate in multiple sclerosis

2005 ◽  
Vol 11 (4) ◽  
pp. 447-449 ◽  
Author(s):  
M P Sormani ◽  
P Bruzzi ◽  
G Comi ◽  
M Filippi
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Glatiramer Acetate ◽  
Resonance Imaging ◽  
Relapsing Remitting ◽  
Patient Heterogeneity ◽  
Magnetic Resonance Imaging Mri ◽  
Using Data ◽  
Measured Response

We investigated the distribution of the magnetic resonance imaging (MRI)-measured response to glatiramer acetate (GA) treatment in multiple sclerosis (MS) using data from a clinical trial of relapsing=remitting (RR) MS. A fixed and a random effects model were used to quantify the between-patient heterogeneity in treatment response, expressed as new enhancing lesion percentage reduction. In 95% of the patients, lesion reduction due to treatment was estimated to range between -20% and -54%, indicating a rather homogeneous effect of GA on MRI-measured disease activity in RRMS.

Molecular detection of Parachlamydia-like organisms in cerebrospinal fluid of patients with multiple sclerosis

2008 ◽  
Vol 14 (4) ◽  
pp. 564-566 ◽  
Author(s):  
C Contini ◽  
S Seraceni ◽  
R Cultrera ◽  
M Castellazzi ◽  
E Granieri ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Activity ◽  
Neurological Disorders ◽  
Chlamydia Pneumoniae ◽  
Molecular Detection ◽  
Resonance Imaging ◽  
Relapsing Remitting ◽  
Polymerase Chain ◽  
Magnetic Resonance Imaging Mri

The presence of Chlamydia-like organism DNA was investigated by polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) samples from 27 patients previously found positive for Chlamydia pneumoniae DNA: 12 with multiple sclerosis (MS), grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, 8 with other inflammatory neurological disorders and 7 with non-inflammatory neurological disorders. PCR evidence of Chlamydia-like organisms in CSF was observed only in two relapsing–remitting MS patients with clinical and MRI disease activity. These findings suggest a possible association between C. pneumoniae and Chlamydia-like organism brain infections as a cofactor in MS development.

scholarly journals Myelin repair: the role of stem and precursor cells in multiple sclerosis

2007 ◽  
Vol 363 (1489) ◽  
pp. 171-183 ◽  
Author(s):  
Siddharthan Chandran ◽  
David Hunt ◽  
Alexis Joannides ◽  
Chao Zhao ◽  
Alastair Compston ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Dominant Role ◽  
Experimental Studies ◽  
Precursor Cells ◽  
Potential Contribution ◽  
Myelin Repair ◽  
Relapsing Remitting ◽  
Clinical Biology ◽  
Progressive Stage

Multiple sclerosis is the most common potential cause of neurological disability in young adults. The disease has two distinct clinical phases, each reflecting a dominant role for separate pathological processes: inflammation drives activity during the relapsing–remitting stage and axon degeneration represents the principal substrate of progressive disability. Recent advances in disease-modifying treatments target only the inflammatory process. They are ineffective in the progressive stage, leaving the science of disease progression unsolved. Here, the requirement is for strategies that promote remyelination and prevent axonal loss. Pathological and experimental studies suggest that these processes are tightly linked, and that remyelination or myelin repair will both restore structure and protect axons. This review considers the basic and clinical biology of remyelination and the potential contribution of stem and precursor cells to enhance and supplement spontaneous remyelination.

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