EpimiRTherapy | Using human tissue to translate microRNA-based therapies for epilepsy

Summary
The overall research aim of EpimiRTherapy is to elucidate the mechanism of a novel disease-modifying therapy for epilepsy at single cell resolution in the human brain. MicroRNAs are short non-coding RNAs which regulate protein levels in the brain. Certain microRNAs are strongly associated with epilepsy and their knockdown, using antisense molecules called ‘antagomirs’, has anti-seizure effects in rodents. Antagomir targeting microRNA-134 (ant-134) is a particularly promising disease-modifying treatment for epilepsy, which could meet an urgent clinical need. However, antagomirs to treat neurological disease have never been tested in humans due to limited translational evidence. EpimiRTherapy, for the first time, fills this gap: I will use state-of-the-art techniques to produce human brain slices from tissue surgically resected during temporal lobectomies for epilepsy. I will use a combination of molecular techniques (acquired at the host lab in RCSI and through secondment to ICL) and electrophysiology, my core expertise, to determine the impact of ant-134 on the biophysical and transcriptional landscapes of human tissue and a network and single neuron level. This will be complemented with cutting edge systems modelling and imaging techniques acquired through collaborations. This fellowship, through advanced interdisciplinary and intersectoral training, will serve as a launchpad for reaching a position of professional independence and maturity, whilst at the same time facilitating a transfer of knowledge between myself, the host and the collaborators, by bringing cutting edge electrophysiology and human tissue processing techniques to RCSI and addressing an urgent and unmet clinical need for novel epilepsy treatments.
Unfold all
/
Fold all
More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/840262
Start date: 01-12-2019
End date: 30-11-2021
Total budget - Public funding: 184 590,72 Euro - 184 590,00 Euro
Cordis data

Original description

The overall research aim of EpimiRTherapy is to elucidate the mechanism of a novel disease-modifying therapy for epilepsy at single cell resolution in the human brain. MicroRNAs are short non-coding RNAs which regulate protein levels in the brain. Certain microRNAs are strongly associated with epilepsy and their knockdown, using antisense molecules called ‘antagomirs’, has anti-seizure effects in rodents. Antagomir targeting microRNA-134 (ant-134) is a particularly promising disease-modifying treatment for epilepsy, which could meet an urgent clinical need. However, antagomirs to treat neurological disease have never been tested in humans due to limited translational evidence. EpimiRTherapy, for the first time, fills this gap: I will use state-of-the-art techniques to produce human brain slices from tissue surgically resected during temporal lobectomies for epilepsy. I will use a combination of molecular techniques (acquired at the host lab in RCSI and through secondment to ICL) and electrophysiology, my core expertise, to determine the impact of ant-134 on the biophysical and transcriptional landscapes of human tissue and a network and single neuron level. This will be complemented with cutting edge systems modelling and imaging techniques acquired through collaborations. This fellowship, through advanced interdisciplinary and intersectoral training, will serve as a launchpad for reaching a position of professional independence and maturity, whilst at the same time facilitating a transfer of knowledge between myself, the host and the collaborators, by bringing cutting edge electrophysiology and human tissue processing techniques to RCSI and addressing an urgent and unmet clinical need for novel epilepsy treatments.

Status

CLOSED

Call topic

MSCA-IF-2018

Update Date

28-04-2024
Images
No images available.
Geographical location(s)
Structured mapping
Unfold all
/
Fold all
Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2018
MSCA-IF-2018