Multiple Sclerosis Society

About: Multiple Sclerosis Society is a nonprofit organization based out in London, United Kingdom. It is known for research contribution in the topics: Multiple sclerosis & Myelin. The organization has 238 authors who have published 238 publications receiving 9179 citations. The organization is also known as: MS Society.

M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination

Abstract: In this study, the authors show that oligodendrocyte differentiation and remyelination after a CNS lesion coincides with a switch in microglial/macrophage polarization from a pro-inflammatory, M1, phenotype to an anti-inflammatory, M2, phenotype. This M2-dependant effect was in part mediated by secretion of the TGFβ family member, Activin-A.

Cannabinoids control spasticity and tremor in a multiple sclerosis model.

Abstract: Chronic relapsing experimental allergic encephalomyelitis (CREAE) is an autoimmune model of multiple sclerosis1. Although both these diseases are typified by relapsing-remitting paralytic episodes, after CREAE induction by sensitization to myelin antigens1 Biozzi ABH mice also develop spasticity and tremor. These symptoms also occur during multiple sclerosis and are difficult to control. This has prompted some patients to find alternative medicines, and to perceive benefit from cannabis use2. Although this benefit has been backed up by small clinical studies, mainly with non-quantifiable outcomes3,4,5,6,7, the value of cannabis use in multiple sclerosis remains anecdotal. Here we show that cannabinoid (CB) receptor agonism using R(+)-WIN 55,212, Δ9-tetrahydrocannabinol, methanandamide and JWH-133 (ref. 8) quantitatively ameliorated both tremor and spasticity in diseased mice. The exacerbation of these signs after antagonism of the CB1 and CB2 receptors, notably the CB1 receptor, using SR141716A and SR144528 (ref. 8) indicate that the endogenous cannabinoid system may be tonically active in the control of tremor and spasticity. This provides a rationale for patients' indications of the therapeutic potential of cannabis in the control of the symptoms of multiple sclerosis2, and provides a means of evaluating more selective cannabinoids in the future.

Gait and balance impairment in early multiple sclerosis in the absence of clinical disability

Abstract: This study evaluated the gait and balance performance of two clinically distinct groups of recently diagnosed and minimally impaired multiple sclerosis (MS) patients (Expanded Disability Status Scale range 0-2.5), compared to control subjects. Ten MS patients with mild pyramidal signs (Pyramidal Functional Systems 1.0), 10 MS patients with no pyramidal signs (Pyramidal Functional Systems 0) and 20 age- and gender-matched control subjects were assessed using laboratory-based gait analysis and clinical balance measures. Both MS groups demonstrated reduced speed and stride length (P < 0.001), and prolonged double limb support (P <0.02), compared to the control group, along with alterations in the timing of ankle muscle activity, and the pattern of ankle motion during walking, which occurred independent of gait speed. The pyramidal MS group walked with reduced speed (P = 0.03) and stride length (P = 0.04), and prolonged double limb support (P =0.01), compared to the non-pyramidal group. Both MS groups demonstrated concomitant balance impairment, performing poorly on the Functional Reach Test compared to the control group (P <0.05). The identification of incipient gait and balance impairment in MS patients with recent disease onset suggests that motor function may begin to deteriorate in the early stages of the disease, even in the absence of clinical signs of pyramidal dysfunction.

Retinoid X receptor gamma signaling accelerates CNS remyelination

Abstract: The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. We generated a comprehensive transcriptional profile of the separate stages of spontaneous remyelination that follow focal demyelination in the rat CNS and found that transcripts that encode the retinoid acid receptor RXR-γ were differentially expressed during remyelination. Cells of the oligodendrocyte lineage expressed RXR-γ in rat tissues that were undergoing remyelination and in active and remyelinated multiple sclerosis lesions. Knockdown of RXR-γ by RNA interference or RXR-specific antagonists severely inhibited oligodendrocyte differentiation in culture. In mice that lacked RXR-γ, adult oligodendrocyte precursor cells efficiently repopulated lesions after demyelination, but showed delayed differentiation into mature oligodendrocytes. Administration of the RXR agonist 9-cis-retinoic acid to demyelinated cerebellar slice cultures and to aged rats after demyelination caused an increase in remyelinated axons. Our results indicate that RXR-γ is a positive regulator of endogenous oligodendrocyte precursor cell differentiation and remyelination and might be a pharmacological target for regenerative therapy in the CNS.