[HTML][HTML] Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome
CR Jonak, EV Pedapati, LM Schmitt, SA Assad… - Journal of …, 2022 - Springer
Journal of Neurodevelopmental Disorders, 2022•Springer
Abstract Background Fragile X syndrome (FXS) is the most common inherited form of
neurodevelopmental disability. It is often characterized, especially in males, by intellectual
disability, anxiety, repetitive behavior, social communication deficits, delayed language
development, and abnormal sensory processing. Recently, we identified
electroencephalographic (EEG) biomarkers that are conserved between the mouse model of
FXS (Fmr1 KO mice) and humans with FXS. Methods In this report, we evaluate small …
neurodevelopmental disability. It is often characterized, especially in males, by intellectual
disability, anxiety, repetitive behavior, social communication deficits, delayed language
development, and abnormal sensory processing. Recently, we identified
electroencephalographic (EEG) biomarkers that are conserved between the mouse model of
FXS (Fmr1 KO mice) and humans with FXS. Methods In this report, we evaluate small …
Background
Fragile X syndrome (FXS) is the most common inherited form of neurodevelopmental disability. It is often characterized, especially in males, by intellectual disability, anxiety, repetitive behavior, social communication deficits, delayed language development, and abnormal sensory processing. Recently, we identified electroencephalographic (EEG) biomarkers that are conserved between the mouse model of FXS (Fmr1 KO mice) and humans with FXS.
Methods
In this report, we evaluate small molecule target engagement utilizing multielectrode array electrophysiology in the Fmr1 KO mouse and in humans with FXS. Neurophysiologic target engagement was evaluated using single doses of the GABAB selective agonist racemic baclofen (RBAC).
Results
In Fmr1 KO mice and in humans with FXS, baclofen use was associated with suppression of elevated gamma power and increase in low-frequency power at rest. In the Fmr1 KO mice, a baclofen-associated improvement in auditory chirp synchronization was also noted.
Conclusions
Overall, we noted synchronized target engagement of RBAC on resting state electrophysiology, in particular the reduction of aberrant high frequency gamma activity, across species in FXS. This finding holds promise for translational medicine approaches to drug development for FXS, synchronizing treatment study across species using well-established EEG biological markers in this field.
Trial registration
The human experiments are registered under NCT02998151.
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