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      Personalized Medicine Using Cutting Edge Technologies for Genetic Epilepsies

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          Abstract

          Epilepsy is the most common chronic neurologic disorder in the world, affecting 1-2% of the population. Besides, 30% of epilepsy patients are drug-resistant. Genomic mutations seem to play a key role in its etiology and knowledge of strong effect mutations in protein structures might improve prediction and the development of efficacious drugs to treat epilepsy. Several genetic association studies have been undertaken to examine the effect of a range of candidate genes for resistance. Although, few studies have explored the effect of the mutations into protein structure and biophysics in the epilepsy field. Much work remains to be done, but the plans made for exciting developments will hold therapeutic potential for patients with drug-resistance. In summary, we provide a critical review of the perspectives for the development of individualized medicine for epilepsy based on genetic polymorphisms/mutations in light of core elements such as transcriptomics, structural biology, disease model, pharmacogenomics and pharmacokinetics in a manner to improve the success of trial designs of antiepileptic drugs.

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          Most cited references160

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          The Protein Data Bank.

          The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.
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            Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

            Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts.
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              MicroRNA therapeutics: towards a new era for the management of cancer and other diseases

              MicroRNAs (miRNAs) are small non-coding RNAs that can modulate mRNA expression. Insights into the roles of miRNAs in development and disease have led to the development of new therapeutic approaches that are based on miRNA mimics or agents that inhibit their functions (antimiRs), and the first such approaches have entered the clinic. This Review discusses the role of different miRNAs in cancer and other diseases, and provides an overview of current miRNA therapeutics in the clinic.
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                Author and article information

                Journal
                Curr Neuropharmacol
                Curr Neuropharmacol
                CN
                Current Neuropharmacology
                Bentham Science Publishers
                1570-159X
                1875-6190
                27 May 2021
                27 May 2021
                : 19
                : 6
                : 813-831
                Affiliations
                [1 ]Brazilian Biosciences National Laboratory (LNBio), Center for Research in Energy and Material (CNPEM) , Campinas, , SP , Brazil;
                [2 ]Laboratory of Embryonic Genetic Regulation, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas , Campinas, , SP , Brazil;
                [3 ]Human Genome and Stem-Cell Research Center (HUG-CEL), Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, SP, Brazil
                Author notes
                [* ]Address correspondence to this author at the Brazilian Biosciences National Laboratory (LNBio), Center for Research in Energy and Material (CNPEM), Rua Giuseppe Máximo Scolfaro, 10000, Cidade Universitária, Campinas, SP 13083970, Brazil; Tel: +55 (19) 35182362, Ext: 2623; E-mail: bruno.araujo@ 123456lnbio.cnpem.br
                Article
                CN-19-813
                10.2174/1570159X18666200915151909
                8686309
                32933463
                fabcaa88-4b4b-4d75-bf0b-b3e72dcf17ec
                © 2021 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 09 July 2020
                : 08 August 2020
                : 28 August 2020
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                genetic epilepsy,brain organoids,transcriptome,single-cell sequencing,pharmacogenomics,drug resistance,drug development,antiepileptic drugs

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