Endogenous repair and development inspired therapy of neurodegeneration in progressive multiple sclerosis

In recent years, there has been progress in understanding the etiology and immune mechanisms of multiple sclerosis (MS). however, for most, once the diagnosis is made, significant pathology is already present in the central nervous system (CNS), and in many, this leads to neurodegeneration, which accumulates in disability. although, the mechanisms of such progression are poorly understood, new data suggest lack of remyelination paired with dysfunction of neurons along with stem and progenitor cells as the basis and recent developmental studies suggest that cns repair processes share mechanisms with development. Areas covered: Here, the authors examine the neurodevelopmental processes that may be reactivated to gain a better understanding of regeneration under pathological conditions. Specifically, the authors focus on the molecular framework of these mechanisms, signaling pathways in neuron and oligodendrocyte development, and provide evidence that the activation of these processes can help us design new therapeutic avenues to halt progression. Expert commentary: Accumulating evidence indicates that there is no single mechanism of progression in MS; instead there is heterogeneity in which repair processes are perturbed. Together, this not only poses a challenge for treatment, but also at the benchside, when prioritizing which developmental targets warrant investigation in future trials.