Journal
NEUROTHERAPEUTICS
Volume 18, Issue 2, Pages 1175-1187Publisher
SPRINGER
DOI: 10.1007/s13311-021-01005-w
Keywords
Fragile X syndrome; electroencephalography; biomarker; TAK-063; phosphodiesterase
Funding
- Takeda International-UK, Rare Diseases Therapeutic Area Unit
Ask authors/readers for more resources
This study demonstrates the beneficial effects of the PDE10A inhibitor TAK-063 on normalizing EEG biomarkers in a mouse model of Fragile X syndrome, suggesting potential for further translational treatment development without noticeable side effects.
Fragile X syndrome (FXS) is a genetic neurodevelopmental syndrome characterized by increased anxiety, repetitive behaviors, social communication deficits, delayed language development, and abnormal sensory processing. Recently, we have identified electroencephalographic (EEG) biomarkers that are conserved between the mouse model of FXS (Fmr1 KO mice) and humans with FXS. In this study, we test a specific candidate mechanism for engagement of multielectrode array (MEA) EEG biomarkers in the FXS mouse model. We administered TAK-063, a potent, selective, and orally active phosphodiesterase 10A (PDE10A) inhibitor, to Fmr1 KO mice, and examined its effects on MEA EEG biomarkers. We demonstrate significant dose-related amelioration of inter-trial phase coherence (ITPC) to temporally modulated auditory stimuli by TAK-063 in Fmr1 KO mice. Our data suggest that TAK-063 improves cortical auditory stimulus processing in Fmr1 KO mice, without significantly depressing baseline EEG power or causing any noticeable sedation or behavioral side effects. Thus, the PDE10A inhibitor TAK-063 has salutary effects on normalizing EEG biomarkers in a mouse model of FXS and should be pursued in further translational treatment development.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available