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Chinese summary
Some neurodevelopmental and neuropsychiatric disorders are characterized by intermittent pathological neuronal activity
.
Although gene therapies provide the ability to modulate neuronal excitability, one of the limiting factors is that they cannot distinguish between neurons involved in pathological circuits and "healthy" peripheral or mixed neurons
.
The researchers described a gene therapy strategy that downregulated the excitability of hyperactive neurons in a closed-loop manner, which they tested
in an epilepsy model.
They used a direct early gene promoter in overactive neurons to drive the expression of the Kv1.
1 potassium channel, and only when they showed abnormal activity
.
Epilepsy-related activity reduces the excitability of neurons, and this gene therapy strategy produces long-lasting anti-epileptic effects
without interfering with normal behavior.
Activity-dependent gene therapy is a promising approach
to on-demand cell autonomously therapeutic brain circuit diseases.
Summary in English
Several neurodevelopmental and neuropsychiatric disorders are characterized by intermittent episodes of pathological activity.
Although genetic therapies offer the ability to modulate neuronal excitability, a limiting factor is that they do not discriminate between neurons involved in circuit pathologies and "healthy" surrounding or intermingled neurons.
We describe a gene therapy strategy that down-regulates the excitability of overactive neurons in closed loop, which we tested in models of epilepsy.
We used an immediate early gene promoter to drive the expression of Kv1.
1 potassium channels specifically in hyperactive neurons, and only for as long as they exhibit abnormal activity.
Neuronal excitability was reduced by seizure-related activity, leading to a persistent antiepileptic effect without interfering with normal behaviors.
Activity-dependent gene therapy is a promising on-demand cell-autonomous treatment for brain circuit disorders.
