Epilepsy and the Wnt Signaling Pathway
Abstract
Epileptogenesis is a gradual process by which normal brain transforms into one that sustains seizures. It is instigated by an inciting event (e.g. prolonged seizure called status epilepticus (SE), head injury, infection or stroke). This is followed by a variable (months to years in humans) latent period followed by the emergence of spontaneous seizures, with potential for later mood and learning disabilities. While the latent period is a time during which behavioral seizures are not observed, it is a period of tissue and cellular remodeling that sets up the development of chronic seizure activity, or epilepsy. In this grant, we have drawn expertise from other fields to discover new mechanistic insights into epileptogenesis. In the past year, we have expanded our understanding of molecular mechanisms, specifically Wnt signaling and an altered metabolism in the hippocampus of mice undergoing early epileptogenesis. In doing so, we have uncovered a new therapeutic drug combination that we had been developing for breast cancer treatment aimed at Wnt signaling. Surprisingly, the combination attenuates seizures in two different models of acute seizures as well as in a model of chronic seizure onset. This combination may have efficacy for preventing the onset of chronic seizures that define epileptic progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2016
- Accession Number
- AD1023935
Entities
People
- James Degregori
Organizations
- Anschutz Medical Campus