Jonathan Geiger, PhD, Chester Fritz Distinguished Professor in the Department of Biomedical Sciences, is on a multi-university, multiple principal investigator team that received a four-year R01 grant from the National Institutes of Health (NIH) totaling more than $2.25 million. The grant, titled “Ketogenic Diet and Adenosine: Epigenetics and Antiepileptogenesis,” marks the first time that a faculty member at UND has been the recipient of three simultaneously held R01 grants from the NIH as a principal investigator. NIH R01 grants are considered one of the most prestigious grants for which individuals can apply, and funding for these grants is extremely competitive.
A ketogenic diet is one that promotes the metabolic formation of ketones—organic compounds made via the oxidation of alcohols—by causing the body to use fats, rather than carbohydrates, as its principal energy source. For nearly 100 years, metabolic therapy with a ketogenic diet (KD) has been shown to control seizures in people with epilepsy. More recently, such diets have shown promise in treating pain, increasing longevity, and increasing athletic performance.
The team of investigators includes Detlev Boison, the director of basic and translational research at the Legacy Research Institute in Portland, Ore.; and Susan A. Masino, Vernon Roosa Professor of Applied Science at Trinity College in Hartford, Conn. The three principal investigators have worked closely together and the awarded grant represents a renewal of an NIH R01 grant that the same team held for five years. The current grant is looking to identify and validate key epigenetic mechanisms engaged by metabolic therapy with a KD and pave the way for novel therapeutic opportunities.
“Receiving this grant is very meaningful in multiple ways,” noted Dr. Geiger. “This is a renewal of an NIH R01 grant that Detlev, Susan, and I held for five years, resulting in us publishing over 20 manuscripts, two books, and multiple book chapters. The three of us believe strongly that a metabolic approach might yield new targets for therapeutics against epilepsy. And, we desperately need new targets and therapeutic strategies because one-third of people living with epilepsy are completely resistant to all current anti-epileptic drugs."
The team’s hypothesis is that epigenetic changes in DNA methylation (a process by which methyl groups—portions of molecules containing one carbon atom bonded to three hydrogen atoms—are added to DNA) mobilized by a ketogenic diet provide a therapeutic target for disease prevention and treatment. The project’s approach is unique in that it initiates disease-modifying treatment after disease onset and their approach stresses the rigor and reproducibility of findings across models of epilepsy and between laboratories. The project also is unique in so far as it includes a strategy that aims to restore homeostasis—and thus offer hope for a cure.
Researchers studying epigenetics explore the mechanisms that regulate gene expression and the activation and deactivation of specific genes. Understanding better how the human body can turn genes on and off during growth, aging, and in response to its environment has important implications for the diagnosis and treatment of many diseases including cancer, diabetes, and neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and epilepsy.