Glutamate-gated chloride channel treatment of epilepsy (360G-Wellcome-209807_Z_17_Z)

£456,266

'Pharmacoresistant epilepsy affects approximately 0.3% of the population in developed countries (-200,000 in the UK alone) and represents a major unmet need. Although surgery to remove the seizure focus is effective, it is limited by risks to normal brain function. We have developed a targeted gene therapy strategy based on a modified glutamate-gated chloride channel (eGiuCI) expressed in excitatory neurons using a viral vector. eGiuCI opens in response to extrasynaptic glutamate when excitatory neurons fire excessively, and decreases neuronal excitability. Because the channel is not targeted to synapses, it does not affect normal brain function. We demonstrated the efficacy of eGiuCI in an acute chemoconvulsant model of evoked focal seizures, and in a neocortical model of established epilepsy characterized by spontaneous seizures, using a blind, randomized preclinical trial design. It had no detectable behavioural side effects. For clinical translation we will (i) redesign the construct used; (ii) optimise delivery; and (iii) demonstrate efficacy and tolerability in a model of long-term limbic epilepsy. The proposed work will de-risk the project to attract investment for first-in-patient clinical trials.

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Grant Details

Amount Awarded 456266
Applicant Surname Kullmann
Approval Committee Innovator Awards Advisory Group
Award Date 2018-09-15T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Innovator Award
Internal ID 209807/Z/17/Z
Lead Applicant Prof Dimitri Kullmann
Other Applicant(s) Dr Andreas Lieb
Partnership Value 456266
Planned Dates: End Date 2021-12-30T00:00:00+00:00
Planned Dates: Start Date 2018-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London