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Project grant

Development of a Drosophila-based platform to replace and reduce animal experimentation in epilepsy research

Dr Manolis Fanto

At a glance

Completed
Award date
December 2020 - September 2023
Grant amount
£259,100
Principal investigator
Dr Manolis Fanto
Institute
King's College London

R

  • Replacement
Read the abstract
View the grant profile on GtR

Overview

Why did we fund this project?

This award aims to develop a Drosophila based platform to analyse genetic components of epilepsy replacing the use of some mice in this research area.

The underlying causes of epilepsy are not always clear, although some patients have a hereditary form of epilepsy. These often co-occur with sleep disorders or movement disorders such as ataxia. A large number of potential gene candidates for these hereditary conditions have been identified in genomic studies, and research is ongoing to confirm any causative genes. These studies typically use mice with transgenic models created to determine whether the mutations are linked to seizures. These models are often classified as severe under the UK’s Animals (Scientific Procedures) Act 1986 because of the level of suffering caused. Drosophila has the potential to be used as an alternative model system as approximately 70% of human genes are also conserved in the fly. Based on current thinking, Drosophila are not considered capable of suffering and therefore provide a replacement for the use of vertebrate animals used in research.

Dr Manolis Fanto aims to enable easier uptake of Drosophila in epilepsy research by developing automated, high-throughput methods to assess seizures. These will include assays to analyse both behaviour and neural activation in seizures. Manolis and colleagues will then use these assays to analyse candidate epilepsy genes identified previously in human studies. This analysis will act as a proof-of-principle study to validate the Drosophila platform to replace the use of mouse studies in both basic and clinical epilepsy research.   

Publications

  1. Deneubourg C et al. (2024). Epg5 links proteotoxic stress due to defective autophagic clearance and epileptogenesis in Drosophila and Vici syndrome patients. Autophagy 1–13. doi: 10.1080/15548627.2024.2405956
  2. Roshandel D et al. (2023). SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy. npj Genomic Medicine 8:28. doi: 10.1038/s41525-023-00370-z