Endocrine Abstracts

Re-myelination in the adult CNS has been demonstrated in different experimental models of demyelinating diseases. However, there is no clear evidence that re-myelination is effective in multiple sclerosis (MS), the most diffuse demyelinating disease. Moreover, chronic disabilities in MS are believed to be due to remyelination failure and consequent neuron damage and degeneration. Due to the presence of numerous oligodendrocyte precursors inside demyelination plaques, reasons for remyelination failure are unknown. Data from embryonic development and in vitro studies supports the primary role of thyroid hormone in oligodendrocyte formation from neural precursors and maturation. We have obtained positive results in promoting re-myelination and neuroprotection in chronic experimental allergic encephalomyelitis (EAE), a widely used experimental model of MS, by recruiting progenitors and channelling them into oligodendroglial lineage through administration of thyroid hormone. Experiments performed in rats and confirmed in the primate Callithrix Jacchus have generated a phase 2 clinical trial that is in progress. We have also explored the role of thyroid hormone in regulating neural precursors cells in the subventricular zone of mature brain by in vivo and in vitro experiments (neurosphere assay), with regard to cell cycle and lineage regulation. Finally, we are exploring the possibility that prenatal events disturbing thyroid function, like endocrine disruptors exposure (dioxin family), might affect oligodendrocyte development and susceptibility to demyelinating agents.