化学遗传学技术在癫痫治疗中的探索与展望

目前癫痫的治疗方法尚不完善,药物治疗仍为首选。但仍有高达30%的癫痫患者因药物控制效果不佳或不能耐受药物的不良反应而成为药物难治性癫痫。因此开发药物难治性癫痫治疗的新方法有非常重要的临床意义。目前已有众多研究聚焦于这一领域,其中化学遗传和光遗传学技术能够通过精准地选择治疗靶点控制某一类型神经元的兴奋性,进而通过调控致痫网络而达到控制癫痫发作的作用。而化学遗传学技术又具有相对无创性的优点,更利于临床转化。本综述简要介绍了化学遗传学中应用最广泛的,仅由特定药物激活的受体(DREADDs)技术的机制及其在癫痫治疗中的研究现状;并对该技术今后的临床转化进行展望。

Exploration and prospects of chemogenetics in treatment of epilepsy

At present,the treatment of epilepsy is not perfect,drug treatment is still the first choice,but there are still up to 30%of patients with epilepsy due to poor efficacy of drug control or intolerance of adverse drug reactions.Therefore,it is of great clinical significance to develop new methods for the treatment of drug-resistant epilepsy.Now,many studies have focused on this field,among which chemical genetics and photogenetics can control the excitability of a certain type of neurons by precisely selecting therapeutic targets,and then achieve the effect of controlling epilepsy by regulating epileptogenic network.Chemical genetics technology has the advantage of non-invasive,which is more conducive to clinical transformation.In this paper,the mechanism of the most widely used designer receptors exclusively activated by designer drugs(DREADDs)technology in chemical genetics and its research status in the treatment of epilepsy are briefly reviewed,and the clinical transformation of this technology in the future is prospected.