Topic: CRISPRi

Altered neuronal excitability in neurodevelopmental disorders can have profound implications for adult brain function. Understanding the critical time windows determining the clinical outcomes and lasting changes induced during these periods is therefore crucial. In our mouse model of developmental and epileptic encephalopathy (DEE) harboring a patient-derived Scn2a (p.A263V) mutation that results in a gain-of-function of Nav1.2 channels, Scn2a mutants exhibit a transient increase in excitability of hippocampal pyramidal neurons in vitro during the neonatal period. In vivo, homozygous Scn2a mu

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant disorder caused by an abnormal expansion of the trinucleotide CAG in the coding region of the ATXN2 gene. This is translated into an expanded polyglutamine tract in the ataxin-2 protein, leading to a gain of toxic function affecting especially the neurons. Besides the pathogenic mechanisms triggered by ataxin-2 dysfunction, previous studies showed that abnormally expanded CAG repeats display toxicity already at the RNA level, contributing to disease pathogenesis. Considering these data, it is important to develop therapeutic approac