Marco Ledri

Marco Ledri

Associate Senior Lecturer

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Research

Epilepsy is a devastating neurological disorder characterized by incontrollable synchronous neuronal activity, which clinically manifests as epileptic seizures. Epilepsy usually develops after an initial insult, such as head trauma or stroke, which trigger the epileptogenic process. During epileptogenesis, the affected brain regions undergo multiple changes in connectivity and gene expression, and between the most affected genes are those responsible for network inhibition. These include genes coding for GABA and endocannabinoid receptors, which are usually downregulated during epileptogenesis, opening up the possibility of interfering with their expression by gene therapy approaches to block the development of recurrent seizures. Recent developments in gene editing technologies, after the discovery and application of the bacteria-derived CRISPR-Cas9 system, have opened new avenues for gene therapy. In particular, the possibility of developing a reversible and precise regulatory system for endogenous genes with high spatio-temporal control, overcomes several limitations of the classic gene therapy approaches. Our group's current research aims to develop and apply an on-demand, controllable gene expression technology, based on guide RNAs and a catalytically inactive Cas9, targeting the expression of GABA and CB1 receptors for the control of epileptogenesis. 

UKÄ subject classification

  • Neurosciences
  • Clinical Medicine

Keywords

  • epilepsy
  • CRISPR/Cas9
  • epileptogenesis
  • Gene Therapy
  • viral vectors

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