Tratamiento actual de la esclerosis múltiple / Current therapy of multiple sclerosis

Desde la introducción del interferón beta 1b para el tratamiento de la esclerosis múltiple, el número de medicamentos disponibles para esta enfermedad ha ido aumentando progresivamente. En la actualidad, en España se dispone de 11 medicamentos aprobados, cuyas indicaciones dependen de determinadas características clínicas. En el presente artículo se revisan dichas indicaciones y se hace mención, asimismo, de otros medicamentos sin aprobación oficial, pero de los que hay experiencia en esclerosis múltiple (AU)

Since the introduction of interferon beta 1 b for the treatment of multiple sclerosis, there has been a progressive increase in the number of drugs available for this disease. Currently, 11 drugs have been approved in Spain, and their indications depend on specific clinical characteristics. The present article reviews these indications and also discusses other medications without official approval that have also been used in multiple sclerosis (AU)

Mecanismos básicos de acción del fingolimod en relación con la esclerosis múltiple / Basic mechanisms of action of fingolimod in relation to multiple sclerosis

Introducción. El fingolimod ha sido aprobado recientemente en Europa para el tratamiento de la esclerosis múltiple recidivante. Ejerce su acción mediante la unión a diversos receptores de esfingosina 1 fosfato (S1P). Objetivo. Revisar los mecanismos básicos de acción que pueden relacionarse con la eficacia terapéutica de este fármaco. Desarrollo. El fingolimod actúa como agonista inverso sobre los receptores de S1P, provocando su degradación. Esto dificulta la salida de los ganglios linfáticos de linfocitos T vírgenes y de memoria central, entre ellos los Th17, portadores de los antígenos de superficie CCR7 y CD62L, lo que produce una marcada linfopenia en la sangre periférica debida a redistribución linfoide. La circulación de linfocitos B se ve, asimismo, afectada, y hay efectos complejos sobre otras células inmunitarias. El fármaco penetra en el sistema nervioso central y actúa sobre los receptores de S1P en las células gliales y las neuronas. Los estudios realizados en encefalomielitis autoinmune experimental indican que su eficacia se debe no sólo a la menor entrada de células inflamatorias, sino también a la acción directa, fundamentalmente sobre la astroglía. Conclusiones. La evidencia disponible sugiere que la eficacia lograda con fingolimod en pacientes de esclerosis múltiple está directamente relacionada con la alteración de la circulación de determinadas subploblaciones de linfocitos T y, probablemente, B. Los estudios en modelos animales apuntan la posibilidad de que en pacientes pueda también contribuir a la eficacia un efecto directo sobre las células gliales (AU)

Introduction. Fingolimod has recently been approved for the therapy of relapsing multiple sclerosis. This drug binds to different sphingosine-1-phosphate receptors. Aim. To analyze basic mechanisms of action that can account for the efficacy of this drug in multiple sclerosis. Development. Fingolimod acts as an inverse agonist on sphingosine-1-phosphate receptors, inducing degradation of receptors. On lymphoid circulation, this effect causes retention in lymph nodes of naïve and central memory T cells, including Th17 T lymphocytes, bearing CCR7 and CD62L receptors. As a result, the level of circulating T cells is markedly decreased. B ell circulation is impaired and complex effects on other immune cells are also induced. Fingolimod enters the central nervous system and binds to receptors on glial cells and neurons. In experimental autoimmune encephalomyelitis, the therapeutic efficacy of fingolimod is not only associated with a reduced entry of inflammatory cells into the nervous system, but also with a direct effect mostly on astroglial cells. Conclusions. In multiple sclerosis patients, the available evidence indicates that fingolimod efficacy is directly associated with impairment of circulation of several T cell subsets and possibly B cells. Animal studies raise the possibility that an additional effect on glial cells might also contribute to the clinical efficacy (AU)

[Basic mechanisms of action of fingolimod in relation to multiple sclerosis]. / Mecanismos basicos de accion del fingolimod en relacion con la esclerosis multiple.

INTRODUCTION: Fingolimod has recently been approved for the therapy of relapsing multiple sclerosis. This drug binds to different sphingosine-1-phosphate receptors. AIM: To analyze basic mechanisms of action that can account for the efficacy of this drug in multiple sclerosis. DEVELOPMENT: Fingolimod acts as an inverse agonist on sphingosine-1-phosphate receptors, inducing degradation of receptors. On lymphoid circulation, this effect causes retention in lymph nodes of naive and central memory T cells, including Th17 T lymphocytes, bearing CCR7 and CD62L receptors. As a result, the level of circulating T cells is markedly decreased. B ell circulation is impaired and complex effects on other immune cells are also induced. Fingolimod enters the central nervous system and binds to receptors on glial cells and neurons. In experimental autoimmune encephalomyelitis, the therapeutic efficacy of fingolimod is not only associated with a reduced entry of inflammatory cells into the nervous system, but also with a direct effect mostly on astroglial cells. CONCLUSIONS: In multiple sclerosis patients, the available evidence indicates that fingolimod efficacy is directly associated with impairment of circulation of several T cell subsets and possibly B cells. Animal studies raise the possibility that an additional effect on glial cells might also contribute to the clinical efficacy.