PMID- 37599992
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230823
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 17
DP  - 2023
TI  - Neurodevelopment and early pharmacological interventions in Fragile X Syndrome.
PG  - 1213410
LID - 10.3389/fnins.2023.1213410 [doi]
LID - 1213410
AB  - 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.
CI  - Copyright (c) 2023 Milla, Corral, Rivera, Zuniga, Pino, Nunez-Parra and Cea-Del 
      Rio.
FAU - Milla, Luis A
AU  - Milla LA
AD  - Centro de Investigacion Biomedica y Aplicada (CIBAP), Escuela de Medicina, 
      Facultad de Ciencias Medicas, Universidad de Santiago de Chile, Santiago, Chile.
FAU - Corral, Lucia
AU  - Corral L
AD  - Laboratorio de Neurofisiopatologia, Centro de Investigacion Biomedica y Aplicada 
      (CIBAP), Escuela de Medicina, Facultad de Ciencias Medicas, Universidad de 
      Santiago de Chile, Santiago, Chile.
FAU - Rivera, Jhanpool
AU  - Rivera J
AD  - Laboratorio de Neurofisiopatologia, Centro de Investigacion Biomedica y Aplicada 
      (CIBAP), Escuela de Medicina, Facultad de Ciencias Medicas, Universidad de 
      Santiago de Chile, Santiago, Chile.
FAU - Zuniga, Nolberto
AU  - Zuniga N
AD  - Laboratorio de Neurofisiopatologia, Centro de Investigacion Biomedica y Aplicada 
      (CIBAP), Escuela de Medicina, Facultad de Ciencias Medicas, Universidad de 
      Santiago de Chile, Santiago, Chile.
FAU - Pino, Gabriela
AU  - Pino G
AD  - Laboratorio de Neurofisiopatologia, Centro de Investigacion Biomedica y Aplicada 
      (CIBAP), Escuela de Medicina, Facultad de Ciencias Medicas, Universidad de 
      Santiago de Chile, Santiago, Chile.
FAU - Nunez-Parra, Alexia
AU  - Nunez-Parra A
AD  - Physiology Laboratory, Department of Biology, Faculty of Science, Universidad de 
      Chile, Santiago, Chile.
AD  - Cell Physiology Center, Universidad de Chile, Santiago, Chile.
FAU - Cea-Del Rio, Christian A
AU  - Cea-Del Rio CA
AD  - Laboratorio de Neurofisiopatologia, Centro de Investigacion Biomedica y Aplicada 
      (CIBAP), Escuela de Medicina, Facultad de Ciencias Medicas, Universidad de 
      Santiago de Chile, Santiago, Chile.
LA  - eng
SI  - figshare/10.6084/m9.figshare.23643210.v1
PT  - Journal Article
PT  - Review
DEP - 20230802
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC10433175
OTO - NOTNLM
OT  - Fragile X syndrome
OT  - GABA
OT  - PI3K
OT  - clinical trials
OT  - mGluR
OT  - neurodevelopment
OT  - pharmacological interventions
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/08/21 06:42
MHDA- 2023/08/21 06:43
PMCR- 2023/01/01
CRDT- 2023/08/21 04:39
PHST- 2023/04/28 00:00 [received]
PHST- 2023/07/17 00:00 [accepted]
PHST- 2023/08/21 06:43 [medline]
PHST- 2023/08/21 06:42 [pubmed]
PHST- 2023/08/21 04:39 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2023.1213410 [doi]
PST - epublish
SO  - Front Neurosci. 2023 Aug 2;17:1213410. doi: 10.3389/fnins.2023.1213410. 
      eCollection 2023.