RESUMO
An unmet but urgent medical need is the development of myelin repair promoting therapies for Multiple Sclerosis (MS). Many such therapies have been pre-clinically tested using different models of toxic demyelination such as cuprizone, ethidium bromide, or lysolecithin and some of the therapies already entered clinical trials. However, keeping track on all these possible new therapies and their efficacy has become difficult with the increasing number of studies. In this study, we aimed at summarizing the current evidence on such therapies through a systematic review and at providing an estimate of the effects of tested interventions by a meta-analysis. We show that 88 different therapies have been pre-clinically tested for remyelination. 25 of them (28%) entered clinical trials. Our meta-analysis also identifies 16 promising therapies which did not enter a clinical trial for MS so far, among them Pigment epithelium-derived factor, Plateled derived growth factor, and Tocopherol derivate TFA-12.We also show that failure in bench to bedside translation from certain therapies may in part be attributable to poor study quality. By addressing these problems, clinical translation might be smoother and possibly animal numbers could be reduced.
Assuntos
Esclerose Múltipla/terapia , Células Precursoras de Oligodendrócitos/citologia , Oligodendroglia/citologia , Remielinização/efeitos dos fármacos , Animais , Cuprizona/toxicidade , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/terapia , Etídio/toxicidade , Proteínas do Olho/farmacologia , Lisofosfatidilcolinas/toxicidade , Camundongos , Esclerose Múltipla/patologia , Bainha de Mielina/metabolismo , Bainha de Mielina/patologia , Fatores de Crescimento Neural/farmacologia , Células Precursoras de Oligodendrócitos/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/farmacologia , Serpinas/farmacologia , Tocoferóis/farmacologiaRESUMO
One main pathological hallmark of multiple sclerosis (MS) is demyelination. Novel therapies which enhance myelin repair are urgently needed. Insulin and insulin-like growth factor 1 (IGF-1) have strong functional relationships. Here, we addressed the potential capacity of IGF-1 and insulin to enhance remyelination in an animal demyelination model in vivo. We found that chronic intrathecal infusion of IGF-1 enhanced remyelination after lysolecithin-induced demyelination in the spinal cord of young and aged rats. Aged rats showed a weaker innate remyelination capacity and are therefore a good model for progressive MS which is defined by chronic demyelination. In contrast to IGF-1, Insulin had no effect on remyelination in either age group. Our findings highlight the potential use of IGF-1 as remyelinating therapy for MS, particularly the progressive stage in which chronic demyelination is the hallmark.
