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GluCl as an epileptic seizure autoregulatory Gene therapeutic approach

Objective

This Horizon2020 – Marie Sklodowska Curie Actions – Individual Fellowship grant proposal focuses on the development of a new gene therapy approach targeting intractable epilepsy, with the major aim to achieve autoregulation of seizure detection and termination. For this purpose, a glutamate-gated chloride channel (GluCl; cloned from C. elegans) will be expressed in excitatory neurons in the rodent brain using a viral vector and a human CamKIIα promoter. In response to increased glutamate levels, as present during epileptic seizures, the channel activates and opens a Cl- conductance. This, in turn, inhibits excitatory neurons and causes seizure suppression. As a further advantage, an “add-on” therapeutic approach with the GluCl agonist ivermectin, an approved antihelminthic drug, is available. In principle, the gene therapy could therefore confer both an autoregulatory effect to the transduced brain region and have an external “gain control” exerted by pharmacological modulation.
Taken together, my Fellowship proposal aims to develop a radically new antiepileptic strategy to treat drug-resistant, refractory epilepsy, which affects approximately 1 million people in Europe.

Coordinator

UNIVERSITY COLLEGE LONDON
Net EU contribution
€ 137 591,10
Address
GOWER STREET
WC1E 6BT London
United Kingdom

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Region
London Inner London — West Camden and City of London
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 137 591,10