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A novel closed-loop gene remedy method to deal with mind circuit problems

A novel closed-loop gene remedy method to deal with mind circuit problems

On-demand expression of a gene that inhibits neuronal exercise reduces spontaneous seizures in mice, researchers say. In a brand new examine, Yichen Qiu and colleagues current a closed-loop gene remedy method to deal with mind circuit problems the place solely a subpopulation of neurons is overactive, together with epilepsy.

Spontaneous and intermittent seizures characterize neurodevelopmental and neuropsychiatric problems akin to epilepsy. Though these episodes will be lowered by anti-seizure drugs, virtually a 3rd of epileptic sufferers don’t reply to those therapies. Others, who initially reply favorably, could later develop tolerance. Aside from pharmacological options, a number of gene remedy methods have proven promise. Nonetheless, these strategies are inclined to indiscriminately goal all neurons in a given mind area reasonably than the precise problematic circuits accountable for triggering the episode.

To treatment this drawback, who et al. have developed a gene remedy technique that self-selects pathologically hyperresponsive neurons and down-regulates their excitability in a closed-loop suggestions system. The method makes use of the fos whose expression is up-regulated by neural exercise, together with seizures, to regulate the physique’s exercise. Kcna1 which codes for an inhibitor gene that calms neuronal exercise.

Qiu et al. used an adeno-associated virus vector encoding the fos and Kcna1 to transfect neurons in a mouse mannequin of epilepsy. In periods of intense neuronal exercise, fos inspired the expression of Kcna1however solely in hyperactive neurons and solely throughout their irregular exercise. Based on the outcomes, neuronal excitability was lowered in these cells by seizure-related exercise, offering a persistent antiepileptic impact that doesn’t intervene with regular behaviors. In a associated Perspective article, Kevin Staley discusses this new method in additional element.

Supply :

American Affiliation for the Development of Science (AAAS)

Journal reference:

Qiu, Y. et al. (2022) On-demand cell-autonomous gene remedy for mind circuit problems. Science. doi.org/10.1126/science.abq6656.

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