Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome

被引:1
作者
Norris, Jordan E. [1 ]
Berry-Kravis, Elizabeth M. [2 ]
Harnett, Mark D. [3 ]
Reines, Scott A. [3 ]
Reese, Melody A. [4 ]
Outterson, Abigail H. [2 ]
Michalak, Claire [2 ]
Furman, Jeremiah [2 ]
Gurney, Mark E. [3 ]
Ethridge, Lauren E. [1 ,5 ]
机构
[1] Univ Oklahoma, Dept Psychol, 455 W Lindsey St,Dale Hall Tower,Room 705, Norman, OK 73019 USA
[2] Rush Univ, Med Ctr, Dept Pediat Neurol Sci & Biochem, Chicago, IL USA
[3] Tetra Therapeut, Grand Rapids, MI USA
[4] Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC USA
[5] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Sect Dev & Behav Pediat, Oklahoma City, OK 73104 USA
来源
MOLECULAR AUTISM | 2024年 / 15卷 / 01期
关键词
Biomarker; Fragile X syndrome; Zatolmilast; EEG; Pharmacokinetics; MECHANISMS;
D O I
10.1186/s13229-024-00626-0
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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页数:6
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