Gene Editing and Rett Syndrome: Does It Make the Cut?

Rett syndrome (RTT) is a rare neurogenetic disorder caused by pathogenic variants of the Methyl CpG binding protein 2 () gene. The RTT is characterized by apparent normal early development followed by regression of communicative and fine motor skills. Comorbidities include epilepsy, severe cognitive impairment, and autonomic and motor dysfunction.

Breaking Boundaries in the Brain-Advances in Editing Tools for Neurogenetic Disorders.

Monogenic neurological disorders are devastating, affecting hundreds of millions of people globally and present a substantial burden to individuals, carers, and healthcare systems. These disorders are predominantly caused by inherited or variants that result in impairments to nervous system development, neurodegeneration, or impaired neuronal function. No cure exists for these disorders with many being refractory to medication.

Pre-clinical Investigation of Rett Syndrome Using Human Stem Cell-Based Disease Models.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, mostly caused by mutations in . The disorder mainly affects girls and it is associated with severe cognitive and physical disabilities. Modeling RTT in neural and glial cell cultures and brain organoids derived from patient- or mutation-specific human induced pluripotent stem cells (iPSCs) has advanced our understanding of the pathogenesis of RTT, such as disease-causing mechanisms, disease progression, and cellular and molecular pathology enabling the identification of actionable therapeutic targets.

Genome-wide transcriptomic and proteomic studies of Rett syndrome mouse models identify common signaling pathways and cellular functions as potential therapeutic targets.

The discovery that Rett syndrome is caused by mutations in the MECP2 gene has provided a major breakthrough in our understanding of the disorder. However, despite this, there is still limited understanding of the underlying pathophysiology of the disorder hampering the development of curative treatments. Over the years, a number of animal models have been developed contributing to our knowledge of the role of MECP2 in development and improving our understanding of how subtle expression levels affect brain morphology and function.