Area of Research:

This project addresses two critical needs in the canine epilepsy field, identification of effective treatments and development of validated outcome measures. Specifically, the proposed prospective, placebo-controlled, pilot clinical trial will identify associations between diet and seizures in canines and test FitBark actigraphy as a potential outcome measure to correlate seizure activity with diet.

Primary Mentor:

Cara Westmark, PhD Assistant Professor Department of Neurology School of Medicine & Public Health University of Wisconsin-Madison Ph: (608) 262-9730 E: [email protected]

Mentor Team:

Starr Cameron, BVetMed, DACVIM (Neurology) Clinical Assistant Professor-Small Animal Neurology Department of Medical Sciences School of Veterinary Medicine

Elizabeth Felton, MD, PhD Assistant Professor Department of Neurology School of Medicine & Public Health

Description of Potential Research Project(s):

Companion animals are typically fed single-source chows that are soy-based. These diets are expected to increase seizures, particularly in genetically susceptible patients. A third of canines with epilepsy are refractory to current anti-seizure medications. Altering the diet to treat epilepsy dates back to c. 400 BC when starvation was used to reduce seizures. The classic ketogenic diet (high fat, low carbohydrate, moderate protein) is employed to replace starvation. We plan to test the efficacy of soy-free and ketogenic diets in reducing seizure incidence in client-owned canines. Our research goal is to translate our preclinical findings that demonstrate anti-seizure effects in response to diet into the clinic to benefit companion animals and humans. Specifically, our preliminary data demonstrate that soy- based vivarium chow exacerbates seizures in mouse models of neurological disease. Retrospective analysis of human medical record data demonstrates a strong association between consumption of soy-based infant formula and seizures in children with autism. These data strongly suggest that consumption of single-source, soy- based diets increases seizures. In addition, we recently found a drastic sex-specific (males only) reduction in seizures and altered circadian activity levels in an autism mouse model in response to ketogenic diet. Despite the long-time use and success of the ketogenic diet in treating refractory epilepsy in humans and promising studies in rodents, there are only a handful of published reports testing effects on seizure reduction in canines. The fellow will conduct a prospective, placebo-controlled, pilot clinical trial employing client-owned canines with epilepsy to examine effects of diet on seizures.

Additional Training Opportunities:

The fellow may choose from multiple training opportunities to accomplish their career development goals. Examples include: (1) ICTR KL2 career development seminars, (2) weekly T32 seminars for Molecular Environmental Toxicology (MET), Neuroscience, Nutritional Sciences and Comparative Biosciences training programs, (3) weekly seminars (Neurology Grand Rounds, Morgridge Metabolism Seminars), (4) UW ICTR Fundamentals of Clinical Research Certificate courses (audit: Intro Biostatistics, Intro to Epidemiology, Intro to Clinical Trials I, Intro to Clinical Trials II, Responsible Conduct of Research), and (5) UW ICTR workshops and non-credit courses (Basics of Conducting Clinical Research at UW Madison, Data Monitoring Committee Training, Fundamentals of Clinical Trials, Intro to Principles and Practices of Clinical Research). Mentor training is crucial to assume a faculty position. There will be ample opportunities for the fellow to co-mentor students such as veterinary students in the Summer Scholars Program and undergraduates working in the laboratory.

Dr. Westmark regularly hosts undergraduate researchers in MET, BioSignals (Neuroscience), and Bio152 programs. Dr. Cameron mentors veterinary students in their preclinical and clinical years, as well as veterinary interns and neurology residents. Dr. Felton hosts undergraduate students in Bio152, Neurology 699, and the SURE (Engineering) program. Presentations at conferences are crucial to career development. Dr. Westmark’s laboratory presents at local (Neurology Research Day, Morgridge Metabolism Symposium, Alzheimer’s Disease Research Day) and national conferences (Society for Neuroscience, Gordon Conference on FXS and Autism). Additional national and international conferences that Dr. Felton’s laboratory present at include American Epilepsy Society and the Global Symposium on Ketogenic Therapies.

Contact Information for Interested Potential Trainees:

Cara Westmark, PhD Assistant Professor Department of Neurology School of Medicine & Public Health University of Wisconsin-Madison

Ph: (608) 262-9730 E: [email protected]