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Publications

Journal Article Review Research Support, Non-U.S. Gov't Epublish 8 citations

PubMed: 40358185 DOI: 10.3390/cells14090662

mTORopathies in Epilepsy and Neurodevelopmental Disorders: The Future of Therapeutics and the Role of Gene Editing.

Cells 14(9)

Authors: Marina Ottmann Boff, Fernando Antônio Costa Xavier, Fernando Mendonça Diz, Júlia Budelon Gonçalves, Laura Meireles Ferreira, Jean Zambeli, Douglas Bottega Pazzin, Thales Thor Ramos Previato, Helena Scartassini Erwig, João Ismael Budelon Gonçalves, Fernanda Thays Konat Bruzzo, Daniel Marinowic, Jaderson Costa da Costa, Gabriele Zanirati

Affiliations

  • Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre 90610-000, RS, Brazil. School of Medicine, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre 90619-900, RS, Brazil.
  • Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre 90610-000, RS, Brazil.
  • Graduate Program in Medicine and Health Sciences, School of Medicine, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre 90619-900, RS, Brazil.
  • Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre 90610-000, RS, Brazil. School of Medicine, University of the Valley of the Rio dos Sinos (UNISINOS), São Leopoldo 93022-750, RS, Brazil.
  • Graduate Program in Pediatrics and Child Health, School of Medicine, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre 90619-900, RS, Brazil.
  • Graduate Program in Biomedical Gerontology, School of Medicine, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre 90619-900, RS, Brazil.
  • Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre 90610-000, RS, Brazil. School of Health and Life, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre 90619-900, RS, Brazil.
  • School of Health and Life, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre 90619-900, RS, Brazil.

Abstract

mTORopathies represent a group of neurodevelopmental disorders linked to dysregulated mTOR signaling, resulting in conditions such as tuberous sclerosis complex, focal cortical dysplasia, hemimegalencephaly, and Smith-Kingsmore Syndrome. These disorders often manifest with epilepsy, cognitive impairments, and, in some cases, structural brain anomalies. The mTOR pathway, a central regulator of cell growth and metabolism, plays a crucial role in brain development, where its hyperactivation leads to abnormal neuroplasticity, tumor formation, and heightened neuronal excitability. Current treatments primarily rely on mTOR inhibitors, such as rapamycin, which reduce seizure frequency and tumor size but fail to address underlying genetic causes. Advances in gene editing, particularly via CRISPR/Cas9, offer promising avenues for precision therapies targeting the genetic mutations driving mTORopathies. New delivery systems, including viral and non-viral vectors, aim to enhance the specificity and efficacy of these therapies, potentially transforming the management of these disorders. While gene editing holds curative potential, challenges remain concerning delivery, long-term safety, and ethical considerations. Continued research into mTOR mechanisms and innovative gene therapies may pave the way for transformative, personalized treatments for patients affected by these complex neurodevelopmental conditions.

MeSH

Cells, Genes, Extracellular Vesicles, Epilepsy, Brain, Neoplasms, Neurodevelopmental Disorders, Gene Editing, Tuberous Sclerosis, Exosomes, Therapeutics, Neurodevelopment

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