Glutamate-gated chloride channel treatment of epilepsy (360G-Wellcome-209807_Z_17_Z)
'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.
Where is this data from?
This data was originally published by The Wellcome Trust. If you see something about your organisation or the funding it has received on this page that doesn't look right you can submit a grantee amendment request. You can hover over codes from standard codelists to see the user-friendly name provided by 360Giving.
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 |