Remyelination Therapy for Multiple Sclerosis

Keough, Michael B.; Yong, V. Wee

doi:10.1007/s13311-012-0152-7

Cited by 54 publications

(42 citation statements)

References 133 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Conversely remyelinated axons appear to regain some of the function of normal neurons and some of the cylindrical symmetry in the organization of lipid layers. (Keough and Yong, 2012). This remyelination process could be monitored by measuring the increase in MSA.…”

Section: Discussionmentioning

confidence: 99%

Magnetic susceptibility anisotropy: Cylindrical symmetry from macroscopically ordered anisotropic molecules and accuracy of MRI measurements using few orientations

et al. 2013

View full text Add to dashboard Cite

White matter is an essential component of the central nervous system and is of major concern in neurodegenerative diseases such as multiple sclerosis (MS). Recent MRI studies have explored the unique anisotropic magnetic properties of white matter using susceptibility tensor imaging. However, these measurements are inhibited in practice by the large number of different head orientations needed to accurately reconstruct the susceptibility tensor. Adding reasonable constraints reduces the number of model parameters and can help condition the tensor reconstruction from a small number of orientations. The macroscopic magnetic susceptibility is decomposed as a sum of molecular magnetic polarizabilities, demonstrating that macroscopic order in molecular arrangement is essential to the existence of and symmetry in susceptibility anisotropy and cylindrical symmetry is a natural outcome of an ordered molecular arrangement. Noise propagation in the susceptibility tensor reconstruction is analyzed through its condition number, showing that the tensor reconstruction is highly susceptible to the distribution of acquired subject orientations and to the tensor symmetry properties, with a substantial over- or under-estimation of susceptibility anisotropy in fiber directions not favorably oriented with respect to the acquired orientations. It was found that a careful acquisition of three non-coplanar orientations and the use of cylindrical symmetry guided by diffusion tensor imaging allowed reasonable estimation of magnetic susceptibility anisotropy in certain major white matter tracts in the human brain.

show abstract

Section: Discussionmentioning

confidence: 99%

Magnetic susceptibility anisotropy: Cylindrical symmetry from macroscopically ordered anisotropic molecules and accuracy of MRI measurements using few orientations

et al. 2013

View full text Add to dashboard Cite

show abstract

“…from the inflammatory environment Keough and Yong, 2013]. Ultimately, axonal transection or neural death results in irreversible functional deficits.…”

Section: Introductionmentioning

confidence: 99%

Alemtuzumab in the treatment of multiple sclerosis: key clinical trial results and considerations for use

Havrdová

Horáková

Kovářová

2015

Ther Adv Neurol Disord

152

129

View full text Add to dashboard Cite

Alemtuzumab is a humanized monoclonal antibody therapy that has recently been approved in over 30 countries for patients with active relapsing-remitting multiple sclerosis. It acts by targeting CD52, an antigen primarily expressed on T and B lymphocytes, resulting in their depletion and subsequent repopulation. The alemtuzumab clinical development program used an active comparator, subcutaneous interferon beta-1a, to show that alemtuzumab is a highly efficacious disease-modifying therapy, with benefits on relapses, disability outcomes, and freedom from clinical disease and magnetic resonance imaging activity. The safety profile was consistent across studies and no new safety signals have emerged during follow-up in the extension study. Infusion-associated reactions are common with alemtuzumab, but rarely serious. Infection incidence was elevated with alemtuzumab in clinical studies; most infections were mild or moderate in severity. Autoimmune adverse events occurred in approximately a third of patients, manifesting mainly as thyroid disorders, and less frequently as immune thrombocytopenia or nephropathy. A comprehensive monitoring program lasting at least 4 years after the last alemtuzumab dose allows early detection and effective management of autoimmune adverse events. Further experience with alemtuzumab in the clinic will provide needed long-term data.

show abstract

“…All currently available medications for MS primarily target the aberrant immune component of the disease and, while effective at reducing relapses, do not markedly delay disease progression. The next generation of therapeutic strategies for the management of MS will integrate advances in immunomodulation with the enhancement of endogenous remyelination in order to prevent both relapses and progression 6 .…”

Section: Introductionmentioning

confidence: 99%

Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin

Keough

Jensen

2015

JoVE

Self Cite

View full text Add to dashboard Cite

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system characterized by plaque formation containing lost oligodendrocytes, myelin, axons, and neurons. Remyelination is an endogenous repair mechanism whereby new myelin is produced subsequent to proliferation, recruitment, and differentiation of oligodendrocyte precursor cells into myelin-forming oligodendrocytes, and is necessary to protect axons from further damage. Currently, all therapeutics for the treatment of multiple sclerosis target the aberrant immune component of the disease, which reduce inflammatory relapses but do not prevent progression to irreversible neurological decline. It is therefore imperative that remyelination-promoting strategies be developed which may delay disease progression and perhaps reverse neurological symptoms. Several animal models of demyelination exist, including experimental autoimmune encephalomyelitis and curprizone; however, there are limitations in their use for studying remyelination. A more robust approach is the focal injection of toxins into the central nervous system, including the detergent lysolecithin into the spinal cord white matter of rodents. In this protocol, we demonstrate that the surgical procedure involved in injecting lysolecithin into the ventral white matter of mice is fast, cost-effective, and requires no additional materials than those commercially available. This procedure is important not only for studying the normal events involved in the remyelination process, but also as a pre-clinical tool for screening candidate remyelination-promoting therapeutics.

show abstract

Remyelination Therapy for Multiple Sclerosis

Cited by 54 publications

References 133 publications

Magnetic susceptibility anisotropy: Cylindrical symmetry from macroscopically ordered anisotropic molecules and accuracy of MRI measurements using few orientations

Magnetic susceptibility anisotropy: Cylindrical symmetry from macroscopically ordered anisotropic molecules and accuracy of MRI measurements using few orientations

Alemtuzumab in the treatment of multiple sclerosis: key clinical trial results and considerations for use

Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin

Contact Info

Product

Resources

About