Manisha N. Patel, PhD – University of Colorado
Kelly G. Knupp, MD – Children’s Hospital Colorado
$150,000 TWO YEAR RESEARCH AWARD
Dravet syndrome (DS) is a catastrophic developmental and epileptic encephalopathy characterized by intractable early-life seizures, and debilitating comorbidities such as cognitive deficits, developmental delay, sleep disturbances, progressive movement abnormalities and increased risk of sudden unexpected death in epilepsy. Our recent work in a zebrafish model of DS suggests that energy usage at the cell level may be disturbed in DS which forms the basis of this project. It is hypothesized that DS patients will display energy defects which will be reflected in their immortalized blood cells to derive metabolic information. The goal of this proposal is to determine if immortalized blood cells (lymphoblast cell lines or LCLs) from DS patients show energy changes compared to age- and gender-matched controls (including unaffected siblings). We will create LCLs from DS patients and control individuals. We propose to test these LCLs for alterations in energy metabolism using assays which are ongoing in our laboratory. Dr. Kelly Knupp has over 110 DS patients in her clinical care and Dr. Manisha Patel’s laboratory routinely conducts metabolism-based assays in specimens from epilepsy models (mice, rats and zebrafish). This research can demonstrate if and how energy metabolism is altered in DS patients and provide a resource of patient-specific LCLs which can be tested for identification of new drugs, diets and treatment responses for DS and its comorbidities.
