Neurodevelopment and early pharmacological interventions in Fragile X Syndrome

Frontiers in Neuroscience

Neuroscience

Luis A. Milla¹  Jhanpool Rivera²  Nolberto Zuñiga²  Christian A. Cea-Del Rio²  Gabriela Pino²  Lucia Corral²  Alexia Nunez-Parra³ 

[1] Centro de Investigacion Biomedica y Aplicada (CIBAP), Escuela de Medicina, Facultad de Ciencias Medicas, Universidad de Santiago de Chile, Santiago, Chile;Laboratorio de Neurofisiopatologia, Centro de Investigacion Biomedica y Aplicada (CIBAP), Escuela de Medicina, Facultad de Ciencias Medicas, Universidad de Santiago de Chile, Santiago, Chile;Physiology Laboratory, Department of Biology, Faculty of Science, Universidad de Chile, Santiago, Chile;Cell Physiology Center, Universidad de Chile, Santiago, Chile;

关键词: neurodevelopment;    Fragile X syndrome;    clinical trials;    pharmacological interventions;    GABA;    mGluR;    PI3K;   

DOI  :  10.3389/fnins.2023.1213410

 received in 2023-04-28, accepted in 2023-07-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

Fragile X Syndrome (FXS) is a neurodevelopmental disorder and the leading monogenic cause of autism and intellectual disability. For years, several efforts have been made to develop an effective therapeutic approach to phenotypically rescue patients from the disorder, with some even advancing to late phases of clinical trials. Unfortunately, none of these attempts have completely succeeded, bringing urgency to further expand and refocus research on FXS therapeutics. FXS arises at early stages of postnatal development due to the mutation and transcriptional silencing of the Fragile X Messenger Ribonucleoprotein 1 gene (FMR1) and consequent loss of the Fragile X Messenger Ribonucleoprotein (FMRP) expression. Importantly, FMRP expression is critical for the normal adult nervous system function, particularly during specific windows of embryogenic and early postnatal development. Cellular proliferation, migration, morphology, axonal guidance, synapse formation, and in general, neuronal network establishment and maturation are abnormally regulated in FXS, underlying the cognitive and behavioral phenotypes of the disorder. In this review, we highlight the relevance of therapeutically intervening during critical time points of development, such as early postnatal periods in infants and young children and discuss past and current clinical trials in FXS and their potential to specifically target those periods. We also discuss potential benefits, limitations, and disadvantages of these pharmacological tools based on preclinical and clinical research.

【 授权许可】

Unknown   
Copyright © 2023 Milla, Corral, Rivera, Zuñiga, Pino, Nunez-Parra and Cea-Del Rio.