scholarly journals Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study

2021 ◽  
pp. 135245852110249
Author(s):  
Hans-Peter Hartung ◽  
Tobias Derfuss ◽  
Bruce AC Cree ◽  
Maria Pia Sormani ◽  
Krzysztof Selmaj ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Brain Atrophy ◽  
Magnetization Transfer ◽  
Brain Magnetic Resonance Imaging ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Magnetization Transfer Ratio ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Transfer Ratio

Background: The envelope protein of human endogenous retrovirus W (HERV-W-Env) is expressed by macrophages and microglia, mediating axonal damage in chronic active MS lesions. Objective and Methods: This phase 2, double-blind, 48-week trial in relapsing-remitting MS with 48-week extension phase assessed the efficacy and safety of temelimab; a monoclonal antibody neutralizing HERV-W-Env. The primary endpoint was the reduction of cumulative gadolinium-enhancing T1-lesions in brain magnetic resonance imaging (MRI) scans at week 24. Additional endpoints included numbers of T2 and T1-hypointense lesions, magnetization transfer ratio, and brain atrophy. In total, 270 participants were randomized to receive monthly intravenous temelimab (6, 12, or 18 mg/kg) or placebo for 24 weeks; at week 24 placebo-treated participants were re-randomized to treatment groups. Results: The primary endpoint was not met. At week 48, participants treated with 18 mg/kg temelimab had fewer new T1-hypointense lesions ( p = 0.014) and showed consistent, however statistically non-significant, reductions in brain atrophy and magnetization transfer ratio decrease, as compared with the placebo/comparator group. These latter two trends were sustained over 96 weeks. No safety issues emerged. Conclusion: Temelimab failed to show an effect on features of acute inflammation but demonstrated preliminary radiological signs of possible anti-neurodegenerative effects. Current data support the development of temelimab for progressive MS. Trial registration: CHANGE-MS: ClinicalTrials.gov: NCT02782858, EudraCT: 2015-004059-29; ANGEL-MS: ClinicalTrials.gov: NCT03239860, EudraCT: 2016-004935-18

A fast B1-mapping method for the correction and normalization of magnetization transfer ratio maps at 3 T

NeuroImage ◽  
2010 ◽  
Vol 49 (4) ◽  
pp. 3015-3026 ◽  
Author(s):  
Steffen Volz ◽  
Ulrike Nöth ◽  
Anna Rotarska-Jagiela ◽  
Ralf Deichmann
Keyword(s):  
Magnetization Transfer ◽  
Mapping Method ◽  
Magnetization Transfer Ratio ◽  
Transfer Ratio ◽  
B1 Mapping

Cervical cord magnetization transfer ratio and clinical changes over 18 months in patients with relapsing-remitting multiple sclerosis: a preliminary study

2006 ◽  
Vol 12 (5) ◽  
pp. 662-665 ◽  
Author(s):  
A Charil ◽  
D Caputo ◽  
R Cavarretta ◽  
M P Sormani ◽  
P Ferrante ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Magnetization Transfer ◽  
Small Sample ◽  
Cervical Cord ◽  
Magnetization Transfer Ratio ◽  
Short Term ◽  
Disease Evolution ◽  
Transfer Ratio ◽  
Relapsing Remitting

Background Magnetization transfer ratio (MTR) permits the quantitative estimation of cervical cord tissue damage in patients with multiple sclerosis (MS). Objective To determine whether a single time-point MTR scan of the cervical cord is associated with short-term disease evolution in patients with relapsing-remitting (RR) MS. Methods Using a 1.5-T magnetic resonance imaging (MRI) system with a tailored cervical cord phased array coil, fast short-tau inversion recovery (fast-STIR) and MTR scans were obtained from 14 untreated patients with RRMS at baseline. Cervical cord MTR histograms were derived. Over the 18- month follow-up period, relapse rate was measured and disability assessed by the Expanded Disability Status Scale (EDSS) score. Results Average cervical cord MTR was correlated with relapse rate ( r= -0.56, P = 0.037). A moderate correlation ( r values ranging from -0.33 to -0.36) between baseline cervical cord MTR metrics and EDSS changes over 18 months was also noted, albeit statistical significance was not reached ( P = 0.26 and 0.21, respectively) perhaps because of the relatively small sample size. Conclusions This study suggests that a ‘snapshot’ MT MRI assessment of the cervical cord may detect cervical cord tissue changes associated with short-term disease evolution in RRMS.

Measurement of magnetization transfer ratio (MTR) from cervical spinal cord: Multicenter reproducibility and variability

2018 ◽  
Vol 49 (6) ◽  
pp. 1777-1785 ◽  
Author(s):  
Benoit Combès ◽  
Laureline Monteau ◽  
Elise Bannier ◽  
Virginie Callot ◽  
Pierre Labauge ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cervical Spinal Cord ◽  
Magnetization Transfer ◽  
Magnetization Transfer Ratio ◽  
Transfer Ratio

Magnetization Transfer Ratio in Peripheral Nerve Tissue

2018 ◽  
Vol 53 (7) ◽  
pp. 397-402 ◽  
Author(s):  
Jennifer Kollmer ◽  
Thorsten Kästel ◽  
Johann M.E. Jende ◽  
Martin Bendszus ◽  
Sabine Heiland
Keyword(s):  
Peripheral Nerve ◽  
Magnetization Transfer ◽  
Nerve Tissue ◽  
Magnetization Transfer Ratio ◽  
Transfer Ratio

scholarly journals Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis

2020 ◽  
Vol 7 (5) ◽  
pp. 799-807 ◽  
Author(s):  
Jennifer Kollmer ◽  
Ute Hegenbart ◽  
Christoph Kimmich ◽  
Ernst Hund ◽  
Jan C. Purrucker ◽  
...  
Keyword(s):  
Magnetization Transfer ◽  
Magnetization Transfer Ratio ◽  
Transthyretin Amyloidosis ◽  
Transfer Ratio ◽  
Hereditary Transthyretin Amyloidosis

scholarly journals T2-Pseudonormalization and Microstructural Characterization in Advanced Stages of Late-infantile Metachromatic Leukodystrophy

2020 ◽  
Author(s):  
Pascal Martin ◽  
Gisela E. Hagberg ◽  
Thomas Schultz ◽  
Klaus Harzer ◽  
Uwe Klose ◽  
...  
Keyword(s):  
Metachromatic Leukodystrophy ◽  
Advanced Disease ◽  
Magnetization Transfer ◽  
Brain Magnetic Resonance Imaging ◽  
Disease Stage ◽  
Magnetization Transfer Ratio ◽  
Water Fraction ◽  
Mri Protocol ◽  
Advanced Disease Stage ◽  
Multimodal Mri

Abstract Purpose T2-weighted signal hyperintensities in white matter (WM) are a diagnostic finding in brain magnetic resonance imaging (MRI) of patients with metachromatic leukodystrophy (MLD). In our systematic investigation of the evolution of T2-hyperintensities in patients with the late-infantile form, we describe and characterize T2-pseudonormalization in the advanced stage of the natural disease course. Methods The volume of T2-hyperintensities was quantified in 34 MRIs of 27 children with late-infantile MLD (median age 2.25 years, range 0.5–5.2 years). In three children with the most advanced clinical course (age >4 years) and for whom the T2-pseudonormalization was the most pronounced, WM microstructure was investigated using a multimodal MRI protocol, including diffusion-weighted imaging, MR spectroscopy (MRS), myelin water fraction (MWF), magnetization transfer ratio (MTR), T1-mapping and quantitative susceptibility mapping. Results T2-hyperintensities in cerebral WM returned to normal in large areas of 3 patients in the advanced disease stage. Multimodal assessment of WM microstructure in areas with T2-pseudonormalization revealed highly decreased values for NAA, neurite density, isotropic water, mean and radial kurtosis, MWF and MTR, as well as increased radial diffusivity. Conclusion In late-infantile MLD patients, we found T2-pseudonormalization in WM tissue with highly abnormal microstructure characterizing the most advanced disease stage. Pathological hallmarks might be a loss of myelin, but also neuronal loss as well as increased tissue density due to gliosis and accumulated storage material. These results suggest that a multimodal MRI protocol using more specific microstructural parameters than T2-weighted sequences should be used when evaluating the effect of treatment trials in MLD.

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