Mastronardi, F. G., L. A. daCruz, H. Wang, J. Boggs, and M. A. Moscarello.
2003. The amount of sonic hedgehog in multiple sclerosis white matter is decreased and cleavage to the signaling peptide is deficient. Mult. Scler. 9:362.
Fortschr Neurol Psychiatr. 2007 Sep;75(9):515-27. [Review of the role of hyperhomocysteinemia and B-vitamin deficiency in neurological and psychiatric disorders--current evidence and preliminary recommendations][Article in German]
Herrmann W, Lorenzl S, Obeid R.
Institut für Klinische Chemie und Laboratoriumsmedizin, Universitätsklinikum des Saarlandes, Kirrberger Strasse, Gebaude 57, 66421 Homburg. email@example.com
Elevated concentration of total homocysteine (Hcy) in plasma (> 12 micromol/l) is a risk factor for several diseases of the central nervous system. Epidemiological studies have shown a dose-dependent relationship between concentrations of Hcy and the risk for neurodegenerative diseases. Hcy is a marker for B-vitamin deficiency (folate, B12, B6). Hyperhomocysteinemia (HHcy) causes hypomethylation which is an important mechanism that links Hcy to dementia. Supplementation with vitamins B aims at reducing the risk of neurodegenerative diseases. Current evidence suggests that Hcy-lowering treatment has a positive effect for the secondary and primary prevention of stroke. HHcy is very common in patients with Parkinson disease particularly those who receive L-dopa treatment. Furthermore, a positive association has been reported between HHcy and multiple sclerosis. Moreover, HHcy and vitamin B deficiency are reported to have a causal role in depression, and epilepsy. In addition several anti-epileptic drugs cause secondary HHcy. Therefore, sufficient intakes of the vitamins are recommended for patients who have already developed neuropsychiatric diseases. Vitamin B deficiency should be suspected in children with development disorders, failure to thrive and unexplained neurological manifestations. Elderly people are also an important at-risk group where vitamin B deficiency and HHcy have been linked to neurodegenerative diseases. Treatment with folate, B12, and B6 can improve cerebral function. Preventive vitamin B supplementation and sufficient intake seem very important for secondary and primary prevention of neuropsychiatric disorders, especially in subjects with a low intake or status of the vitamins.
Mult Scler. 2007 Jun;13(5):596-609. Epub 2007 Feb 9.
Synergy between paclitaxel plus an exogenous methyl donor in the suppression of murine demyelinating diseases.Mastronardi FG, Tsui H, Winer S, Wood DD, Selvanantham T, Galligan C, Fish EN, Dosch HM, Moscarello MA.
Department of Structural Biology and Biochemistry, The Hospital for Sick Children, University Health Network, Toronto, Ontario, Canada. firstname.lastname@example.org
Progressive demyelination in multiple sclerosis (MS) reflects the negative balance between myelin damage and repair due to physical and molecular barriers, such as astrocytic glial scars, between oligodendrocytes and target neurons. In this paper, we show that combination therapy with paclitaxel (Taxol) plus the universal methyl-donor, vitamin B12CN (B12CN), dramatically limits progressive demyelination, and enhances remyelination in several independent, immune and nonimmune, in vivo and in vitro model systems. Combination therapy significantly reduced clinical signs of EAE in SJL mice, as well as the spontaneously demyelinating ND4 transgenic mouse. Astrocytosis was normalised in parallel to ultrastructural and biochemical evidence of remyelination. The combination therapy suppressed T cell expansion, reduced IFN-gamma, while enhancing IFN-beta and STAT-1 expression, STAT-1 phosphorylation and methylation of STAT-1 and MBP in the brain. Paclitaxel/B12CN has nearly identical effects to the previously described combination of IFN-beta/ B12CN, whose clinical usefulness is transient because of IFN-neutralising antibodies, not observed (or expected) with the present drug combination. This report provides a mechanistic foundation for the development of a new therapeutic strategy in humans with MS.
Lancet Neurol. 2006 Nov;5(11):949-60.
Vitamin B12, folic acid, and the nervous system.Reynolds E.
Institute of Epileptology, King's College, Denmark Hill Campus, Cutcombe Road, London, SE5 6PJ, UK. email@example.com
There are many reasons for reviewing the neurology of vitamin-B12 and folic-acid deficiencies together, including the intimate relation between the metabolism of the two vitamins, their morphologically indistinguishable megaloblastic anaemias, and their overlapping neuropsychiatric syndromes and neuropathology, including their related inborn errors of metabolism. Folates and vitamin B12 have fundamental roles in CNS function at all ages, especially the methionine-synthase mediated conversion of homocysteine to methionine, which is essential for nucleotide synthesis and genomic and non-genomic methylation. Folic acid and vitamin B12 may have roles in the prevention of disorders of CNS development, mood disorders, and dementias, including Alzheimer's disease and vascular dementia in elderly people.
Metab Brain Dis. 2006 Sep;21(2-3):121-37. Epub 2006 May 26.
Iron and the folate-vitamin B12-methylation pathway in multiple sclerosis.van Rensburg SJ, Kotze MJ, Hon D, Haug P, Kuyler J, Hendricks M, Botha J, Potocnik FC, Matsha T, Erasmus RT.
Chemical Pathology, National Health Laboratory Service and the University of Stellenbosch, Tygerberg Hospital, PO Box 19113, 7505 Tygerberg, South Africa. firstname.lastname@example.org
Some subjects with multiple sclerosis (MS) present with low blood iron parameters. Anecdotal reports and a single patient study suggest that iron supplementation may be beneficial in these subjects. Myelin is regenerated continually, but prerequisites for this process are iron and a functional folate-vitamin B12-methylation pathway. The aim of this study was to determine iron status, folate and homocysteine in MS subjects, and to evaluate the effect on MS symptoms if deficiencies were addressed. Results: In relapsing-remitting MS subjects, serum iron concentration correlated significantly with age at diagnosis (r=0.49; p=0.008). In Caucasian female MS subjects, serum iron and ferritin concentrations were significantly lower than in matched controls. In a 6-month pilot study, 12 subjects taking a regimen of nutritional supplements designed to promote myelin regeneration, improved significantly neurologically as measured by the Kurzke EDSS (Total Score means 3.50 to 2.45, 29.9%; p=0.021). These were significantly improved (p=0.002) compared to 6 control group patients taking multivitamins (Kurzke Score increased by 13.9% from 4.83 to 5.50). Both groups had significantly reduced homocysteine concentrations at 6 months, suggesting that methylation is necessary but not sufficient for myelin regeneration.
J Neurol Sci. 2005 Jun 15;233(1-2):93-7. Links
Vitamin B12, demyelination, remyelination and repair in multiple sclerosis.Miller A, Korem M, Almog R, Galboiz Y.
Division of Neuroimmunology and Multiple Sclerosis Center, Carmel Medical Center, Haifa 34362, Israel. email@example.com
Multiple Sclerosis (MS) and vitamin B12 deficiency share common inflammatory and neurodegenerative pathophysiological characteristics. Due to similarities in the clinical presentations and MRI findings, the differential diagnosis between vitamin B12 deficiency and MS may be difficult. Additionally, low or decreased levels of vitamin B12 have been demonstrated in MS patients. Moreover, recent studies suggest that vitamin B12, in addition to its known role as a co-factor in myelin formation, has important immunomodulatory and neurotrophic effects. These observations raise the questions of possible causal relationship between the two disorders, and suggest further studies of the need to close monitoring of vitamin B12 levels as well as the potential requirement for supplementation of vitamin B12 alone or in combination with the immunotherapies for MS patients.
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