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

INTRODUCTION: 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.

iPhemap: an atlas of phenotype to genotype relationships of human iPSC models of neurological diseases.

Disease modeling with induced pluripotent stem cells (iPSCs) is creating an abundance of phenotypic information that has become difficult to follow and interpret. Here, we report a systematic analysis of research practices and reporting bias in neurological disease models from 93 published articles. We find heterogeneity in current research practices and a reporting bias toward certain diseases. Moreover, we identified 663 CNS cell-derived phenotypes from 243 patients and 214 controls, which varied by mutation type and developmental stage in vitro We clustered these phenotypes into a taxonomy and characterized these phenotype-genotype relationships to generate a phenogenetic map that revealed novel correlations among previously unrelated genes. We also find that alterations in patient-derived molecular profiles associated with cellular phenotypes, and dysregulated genes show predominant expression in brain regions with pathology. Last, we developed the iPS cell phenogenetic map project atlas (iPhemap), an open submission, online database to continually catalog disease phenotypes. Overall, our findings offer new insights into the phenogenetics of iPSC-derived models while our web tool provides a platform for researchers to query and deposit phenotypic information of neurological diseases.