Tau reduction prevents disease in a mouse model of Dravet syndrome
Ania L. Gheyara MD, PhD, Ravikumar Ponnusamy PhD, Biljana Djukic PhD, Ryan J. Craft BS, Kaitlyn Ho BS, Weikun Guo MS, Mariel M. Finucane PhD, Pascal E. Sanchez PhD, and Lennart Mucke MD
Contributed by Sloka Iyengar
Annals of Neurology, Volume 76, Issue 3, pages 443-456 September 2014 Article first published online: 13 August 2014. DOI: 10.1002/ana.24230
Objective: Reducing levels of the microtubule-associated protein tau has shown promise as a potential treatment strategy for diseases with secondary epileptic features such as Alzheimer disease. We wanted to determine whether tau reduction may also be of benefit in intractable genetic epilepsies.
Results: Tau ablation prevented the high mortality of Dravet mice and reduced the frequency of spontaneous and febrile seizures. It reduced interictal epileptic spikes in vivo and drug-induced epileptic activity in brain slices ex vivo. Tau ablation also prevented biochemical changes in the hippocampus indicative of epileptic activity and ameliorated abnormalities in learning and memory, nest building, and open field behaviors in Dravet mice. Deletion of only 1 Tau allele was sufficient to suppress epileptic activity and improve survival and nesting performance.
Interpretation: Tau reduction may be of therapeutic benefit in Dravet syndrome and other intractable genetic epilepsies.
Subscribe to the ILAE Newsletter
To subscribe, please click on the button below.
Please send me information about ILAE activities and other
information of interest to the epilepsy community