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What Do Effective Treatments for Multiple Sclerosis Tell Us about the Molecular Mechanisms Involved in Pathogenesis?
Department of Neurology, Royal Melbourne Hospital, Royal Parade, Parkville VIC 3050, Australia
School of Medicine, Griffith University, Gold Coast Campus, QLD 4222, Australia
Department of Neurology, Gold Coast Hospital, 108 Nerang Street, Southport QLD 4215, Australia
Melbourne Brain Centre at the Royal Melbourne Hospital, Department of Medicine, University of Melbourne, Royal Parade, Parkville VIC 3010, Australia
* Author to whom correspondence should be addressed.
Received: 2 August 2012; in revised form: 8 September 2012 / Accepted: 12 September 2012 / Published: 4 October 2012
Abstract: Multiple sclerosis is a potentially debilitating disease of the central nervous system. A concerted program of research by many centers around the world has consistently demonstrated the importance of the immune system in its pathogenesis. This knowledge has led to the formal testing of a number of therapeutic agents in both animal models and humans. These clinical trials have shed yet further light on the pathogenesis of MS through their sometimes unexpected effects and by their differential effects in terms of impact on relapses, progression of the disease, paraclinical parameters (MRI) and the adverse events that are experienced. Here we review the currently approved medications for the commonest form of multiple sclerosis (relapsing-remitting) and the emerging therapies for which preliminary results from phase II/III clinical trials are available. A detailed analysis of the molecular mechanisms responsible for the efficacy of these medications in multiple sclerosis indicates that blockade or modulation of both T- and B-cell activation and migration pathways in the periphery or CNS can lead to amelioration of the disease. It is hoped that further therapeutic trials will better delineate the pathogenesis of MS, ultimately leading to even better treatments with fewer adverse effects.
Keywords: multiple sclerosis; treatment; mechanism of action; immunomodulation
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Buzzard, K.A.; Broadley, S.A.; Butzkueven, H. What Do Effective Treatments for Multiple Sclerosis Tell Us about the Molecular Mechanisms Involved in Pathogenesis? Int. J. Mol. Sci. 2012, 13, 12665-12709.
Buzzard KA, Broadley SA, Butzkueven H. What Do Effective Treatments for Multiple Sclerosis Tell Us about the Molecular Mechanisms Involved in Pathogenesis? International Journal of Molecular Sciences. 2012; 13(10):12665-12709.
Buzzard, Katherine A.; Broadley, Simon A.; Butzkueven, Helmut. 2012. "What Do Effective Treatments for Multiple Sclerosis Tell Us about the Molecular Mechanisms Involved in Pathogenesis?" Int. J. Mol. Sci. 13, no. 10: 12665-12709.