This work provides tangible therapeutic strategies that can be used to block epileptogenesis and the development of epilepsy. 

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CURE Epilepsy Discovery: Multi-disciplinary Approach to Uncover New Strategies to Prevent Epilepsy

Key Points:
* For their CURE Epilepsy Multi-disciplinary grant, Dr. Audrey Yee, an epilepsy researcher and clinical neurologist based at the University of Colorado (now at the National Institute of Allergy and Infectious Disease), and Dr. Amy Yee, a breast cancer and Wnt signaling pathway researcher at Tufts University, used their different expertise to investigate novel mechanisms underlying epileptogenesis.
* Utilizing learnings from studies in cancer, the team was able to show that two different biological pathways, the Wnt pathway and the mTOR signaling pathway, are altered during epileptogenesis. Changes in these pathways contribute to an increased susceptibility to seizures. This study is the first to demonstrate the potential relevance of the Wnt signaling pathway in epileptogenesis and epilepsy.
* By revealing biological changes that happen during epileptogenesis, this work provides tangible therapeutic strategies that can be used to block epileptogenesis and the development of epilepsy.

Deep Dive:

In acquired epilepsies, a brain injury following head trauma or status epilepticus (a prolonged seizure) can be followed by a latent period called epileptogenesis. During this period, seizures are not occurring, but the brain is undergoing many changes that render it susceptible to seizures. Scientists want to better understand what happens in the brain during this process with the goal of stopping it and ultimately preventing epilepsy. CURE Epilepsy funded two such scientists, Drs. Amy and Audrey Yee (cousins), who focused their research on two cell signaling pathways and changes that take place during epileptogenesis. ([link removed])

Previous studies have shown that the cellular signaling pathway known as mTOR is widely implicated in some epilepsies. The focus of the current study was to explore both mTOR’s role and biochemical integration with a second biological pathway called the Wnt pathway together as part of the process of epileptogenesis. The Wnt pathway is implicated in cancer so the CURE Epilepsy grant allowed these two cousins to leverage their individual research foci in this innovative study, which led to the discovery of the role Wnt signaling plays in epileptogenesis.  

For their study, the researchers used two types of mouse models, one in which status epilepticus had been chemically induced and the other in which Wnt signaling had been genetically enhanced. To create a complete picture of the mTOR and Wnt signaling pathways during epileptogenesis, the scientists used state-of-the-art techniques to examine the levels of mRNA (molecules that carry the genetic code for protein) and the relevant proteins themselves, including where in the brain they are expressed. The scientists also looked at the balance of chemical messengers known as neurotransmitters and focused on an area of the brain called the hippocampus because of its role in seizure generation and propagation.
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