Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome / Elizabeth M BERRY-KRAVIS ; Mark D HARNETT ; Scott A REINES ; Melody A REESE ; Abigail H OUTTERSON ; Claire MICHALAK ; Jeremiah FURMAN ; Mark E GURNEY ; Lauren E ETHRIDGE in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 47 Titre : Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth M BERRY-KRAVIS, Auteur ; Mark D HARNETT, Auteur ; Scott A REINES, Auteur ; Melody A REESE, Auteur ; Abigail H OUTTERSON, Auteur ; Claire MICHALAK, Auteur ; Jeremiah FURMAN, Auteur ; Mark E GURNEY, Auteur ; Lauren E ETHRIDGE, Auteur Article en page(s) : 47 Langues : Anglais (eng) Mots-clés : Adult  Humans  Male  Middle Aged  Young Adult  Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism  *Electroencephalography  Evoked Potentials  Evoked Potentials, Auditory/drug effects  *Fragile X Syndrome/blood/drug therapy/physiopathology  Biomarker  Eeg  Fragile X syndrome  Pharmacokinetics  Zatolmilast  interests. M.D.H.and S.D.R. are paid consultants to Tetra Therapeutics. M.E.G. is  an employee of TetraTherapeutics, which is a wholly owned subsidiary of Shionogi  & Co., Ltd that has a financial interest in BPN14770. Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is a rare neurodevelopmental disorder caused by a CGG repeat expansion???200 repeats in 5' untranslated region of the FMR1 gene, leading to intellectual disability and cognitive difficulties, including in the domain of communication. A recent phase 2a clinical trial testing BPN14770, a phosphodiesterase 4D inhibitor, showed improved cognition in 30 adult males with FXS on drug relative to placebo. The initial study found significant improvements in clinical measures assessing cognition, language, and daily functioning in addition to marginal improvements in electroencephalography (EEG) results for the amplitude of the N1 event-related potential (ERP) component. These EEG results suggest BPN14770 improved neural hyperexcitability in FXS. The current study investigated the relationship between BPN14770 pharmacokinetics and the amplitude of the N1 ERP component from the initial data. Consistent with the original group-level finding post-period 1 of the study, participants who received BPN14770 in period 1 showed a significant correlation between N1 amplitude and serum concentration of BPN14770 measured at the end of period 1. These findings strengthen the validity of the original result, indicating that BPN14770 improves cognitive performance by modulating neural hyperexcitability. This study represents the first report of a significant correlation between a reliably abnormal EEG marker and serum concentration of a novel pharmaceutical in FXS. En ligne : https://dx.doi.org/10.1186/s13229-024-00626-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 [article] Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome [Texte imprimé et/ou numérique] / Elizabeth M BERRY-KRAVIS, Auteur ; Mark D HARNETT, Auteur ; Scott A REINES, Auteur ; Melody A REESE, Auteur ; Abigail H OUTTERSON, Auteur ; Claire MICHALAK, Auteur ; Jeremiah FURMAN, Auteur ; Mark E GURNEY, Auteur ; Lauren E ETHRIDGE, Auteur . - 47. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 47 Mots-clés : Adult  Humans  Male  Middle Aged  Young Adult  Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism  *Electroencephalography  Evoked Potentials  Evoked Potentials, Auditory/drug effects  *Fragile X Syndrome/blood/drug therapy/physiopathology  Biomarker  Eeg  Fragile X syndrome  Pharmacokinetics  Zatolmilast  interests. M.D.H.and S.D.R. are paid consultants to Tetra Therapeutics. M.E.G. is  an employee of TetraTherapeutics, which is a wholly owned subsidiary of Shionogi  & Co., Ltd that has a financial interest in BPN14770. Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is a rare neurodevelopmental disorder caused by a CGG repeat expansion???200 repeats in 5' untranslated region of the FMR1 gene, leading to intellectual disability and cognitive difficulties, including in the domain of communication. A recent phase 2a clinical trial testing BPN14770, a phosphodiesterase 4D inhibitor, showed improved cognition in 30 adult males with FXS on drug relative to placebo. The initial study found significant improvements in clinical measures assessing cognition, language, and daily functioning in addition to marginal improvements in electroencephalography (EEG) results for the amplitude of the N1 event-related potential (ERP) component. These EEG results suggest BPN14770 improved neural hyperexcitability in FXS. The current study investigated the relationship between BPN14770 pharmacokinetics and the amplitude of the N1 ERP component from the initial data. Consistent with the original group-level finding post-period 1 of the study, participants who received BPN14770 in period 1 showed a significant correlation between N1 amplitude and serum concentration of BPN14770 measured at the end of period 1. These findings strengthen the validity of the original result, indicating that BPN14770 improves cognitive performance by modulating neural hyperexcitability. This study represents the first report of a significant correlation between a reliably abnormal EEG marker and serum concentration of a novel pharmaceutical in FXS. En ligne : https://dx.doi.org/10.1186/s13229-024-00626-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555

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