Promoting Remyelination in Multiple Sclerosis—Recent Advances

Münzel, Eva Jolanda; Williams, Anna

doi:10.1007/s40265-013-0146-8

Cited by 63 publications

(36 citation statements)

References 132 publications

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“…While it is not the aim of this review to cover drugs which are in the pre-clinical stages of development, it is nonetheless important to highlight critical pre-clinical research on MS that has led to several promising approaches shown to potentiate mechanisms of tissue recovery (Deshmukh et al, 2013; Mangas et al, 2010; Munzel and Williams, 2013; Van der Walt et al, 2010). Among these, stem cells possess a therapeutic potential that is distinct from that of small molecules and biologics.…”

Section: Therapiesmentioning

confidence: 99%

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

Mallucci

Peruzzotti-Jametti

Bernstock

et al. 2015

Progress in Neurobiology

128

100

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Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one’s genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis.

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Section: Therapiesmentioning

confidence: 99%

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

Mallucci

Peruzzotti-Jametti

Bernstock

et al. 2015

Progress in Neurobiology

128

100

View full text Add to dashboard Cite

show abstract

“…Evaluation of the integrity of myelin in white matter may be important for the diagnosis and assessment of prognosis in MS. Advanced imaging sequences such as myelin water imaging and magnetization transfer MRI have been used to indirectly assess myelin (Alonso-Oriz et al, 2015), however there is a lack of a robust biomarker for demyelination and remyelination in MS patients (Munzel et al, 2013). It would therefore be a significant achievement to develop and validate an MRI technique for direct imaging of conventionally MR “invisible” myelin and use this to evaluate damage and repair to myelin in vivo.…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance imaging of myelin using ultrashort Echo time (UTE) pulse sequences: Phantom, specimen, volunteer and multiple sclerosis patient studies

et al. 2016

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Clinical magnetic resonance imaging of multiple sclerosis (MS) has focused on indirect imaging of myelin in white matter by detecting signal from protons in the water associated with myelin. Here we show that protons in myelin can be directly imaged using ultrashort echo time (UTE) free induction decay (FID) and imaging sequences on a clinical 3T MR scanner. An adiabatic inversion recovery UTE (IR-UTE) sequence was used to detect signal from myelin and simultaneously suppress signal from water protons. Validation studies were performed on myelin lipid and myelin basic protein (MBP) phantoms in the forms of lyophilized powders as well as suspensions in D2O and H2O. IR-UTE sequences were then used to image MS brain specimens, healthy volunteers, and patients. The T2* of myelin was measured using a UTE FID sequence, as well as UTE and IR- UTE sequences at different TEs. T2* values of ~110–330 μs were measured with UTE FID, as well as with UTE and IR-UTE sequences for myelin powders, myelin-D2O and myelin-H2O phantoms, consistent with selective imaging of myelin protons with IR-UTE sequences. Our studies showed myelin selective imaging of white matter in the brains in vitro and in vivo. Complete or partial signal loss was observed in specimens in areas of the brain with histopathologic evidence of myelin loss, and in the brain of patients with MS.

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“…These cells reside in the perivenous demyelinating lesions which generate distinct inflammatory demyelinated plaques situated within the white matter [25]. MS lesions appear in the white matter inside the visual neuron, basal ganglia, brain stem and spinal cord [26]. White matter cells transmit neural signals from grey matter, where Brain Sci.…”

mentioning

confidence: 99%

Multiple Sclerosis: Immunopathology and Treatment Update

et al. 2017

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The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS.

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Promoting Remyelination in Multiple Sclerosis—Recent Advances

Cited by 63 publications

References 132 publications

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis

Magnetic resonance imaging of myelin using ultrashort Echo time (UTE) pulse sequences: Phantom, specimen, volunteer and multiple sclerosis patient studies

Multiple Sclerosis: Immunopathology and Treatment Update

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