UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Chemical-genetic attenuation of focal neocortical seizures.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    K├Ątzel D, Nicholson E, Schorge S, Walker MC, Kullmann DM
  • Publication date:
    27/05/2014
  • Pagination:
    3847, ?
  • Journal:
    Nat Commun
  • Volume:
    5
  • Status:
    Published online
  • Country:
    England
  • PII:
    ncomms4847
  • Language:
    eng
  • Keywords:
    Acute Disease, Animals, Clozapine, Epilepsies, Partial, Gene Silencing, Genetic Therapy, Humans, Male, Motor Activity, Neocortex, Picrotoxin, Pilocarpine, Rats, Sprague-Dawley, Receptor, Muscarinic M4, Synaptic Transmission
Abstract
Focal epilepsy is commonly pharmacoresistant, and resective surgery is often contraindicated by proximity to eloquent cortex. Many patients have no effective treatment options. Gene therapy allows cell-type specific inhibition of neuronal excitability, but on-demand seizure suppression has only been achieved with optogenetics, which requires invasive light delivery. Here we test a combined chemical-genetic approach to achieve localized suppression of neuronal excitability in a seizure focus, using viral expression of the modified muscarinic receptor hM4Di. hM4Di has no effect in the absence of its selective, normally inactive and orally bioavailable agonist clozapine-N-oxide (CNO). Systemic administration of CNO suppresses focal seizures evoked by two different chemoconvulsants, pilocarpine and picrotoxin. CNO also has a robust anti-seizure effect in a chronic model of focal neocortical epilepsy. Chemical-genetic seizure attenuation holds promise as a novel approach to treat intractable focal epilepsy while minimizing disruption of normal circuit function in untransduced brain regions or in the absence of the specific ligand.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Author
Clinical & Experimental Epilepsy
Author
UCL School of Pharmacy
Author
Clinical & Experimental Epilepsy
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by