Jong M. Rho

SWAMMERDAM LECTURE: Friday March 31st 2023, 16:30-17:30 Prof. dr. Jong Rho

Ketosis and neuroprotection: Mechanisms and implications for diverse and mental health disorders

Host
Prof. Dr. Eleonora Aronica

Zoom link
The Swammerdam lectures will be held live, in case you are not able to attend in person, please contact k.hubregtse@vu.nl

Dr. Rho is a Professor of Neurosciences, Pediatrics and Pharmacology at the University of California, San Diego, and Division Chief of Pediatric Neurology at the Rady Children’s Hospital San Diego. He received an undergraduate degree in molecular biophysics and biochemistry at Yale University, and an M.D. from the University of Cincinnati. Dr. Rho has held prior faculty appointments at the University of Washington (Seattle) and the Seattle Children’s Hospital, the University of California at Irvine, the Barrow Neurological Institute (Phoenix), University of Arizona and Arizona State University, and most recently, the University of Calgary and the Alberta Children’s Hospital. Dr. Rho’s main research interests are the mechanisms underlying the anti-seizure andneuroprotective effects of metabolism-based treatments such as the ketogenic diet. His research activities have been sponsored by research grants from the U.S. National Institutes of Health, Canadian Institutes of Health Research, Brain Canada, anda variety of intramural and extramural public and private sector sources.

The ketogenic diet (KD) is an established nonpharmacologic treatment for medically intractable epilepsy. Initial evidence dating back to the 1920’s demonstrates that metabolism-based therapies, such as the traditional high-fat low-carbohydrate ketogenic diet (KD), can prevent seizures and more recent pre-clinical studies indicate that the KDmay prevent their. Consistently, clinical investigators have reported that >50% of patients with medically intractable epilepsy experience a ≥50% reduction in seizures while on the KD, and 10-20% of such patients can maintain seizure freedom even after weaning from drugs and dietary restrictions. This remarkable efficacy has been consistently observed, even though a KD is unfortunately still often viewed as a “last resort” in cases where there is failure of available drugs and treatments. Clinical use of and research into the mechanisms of the KD have experienced a major resurgence worldwide over the past 25 years. For the epilepsy field, this is likely due to a combination of continued inadequacy of available medical therapies for one-third of patients, rising popularity of diet-based approaches for patients and families, novelinsights into underlying mechanisms, and increasing recognition that the KD and related metabolic therapies have clinical relevance and untapped potential extending well beyond epilepsy – notably, in other neurological and even psychiatric conditions, including but not limited to brain cancer, Parkinson’s and Alzheimer’s diseases, traumatic brain & spinal cord injury, pain, multiple sclerosis, autism spectrum disorder, and bipolar disorder. More recently, less restrictive variations of the KD have emerged as efficacious anti-seizure treatments for both pediatric and adult patients. At the same time, there has been intense research into developing metabolism-based compounds as either alternatives or supplements to dietary therapy such as the anaplerotictripheptanoin, decanoic acid, polyunsaturated fatty acids, and ketone esters. It is now well appreciated that bioenergetic dysfunction – primarily perturbations in mitochondrial function – is associated with most if not all neurological disorders, and the potential of a metabolic therapy like the KD may be significantly underexploited. In this lecture, the fundamental mechanisms that underlie both structural and functional neuroprotective properties of the KD (and notably, ketone bodies) and implications for a growing list of brain and mental health disorders will be discussed.

Link to ONWAR website