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Dr. Douglas Eagles Investigates Cure for Epilepsy

By Theodora Danylevich

No one knows why, but a special diet that mimics the metabolic effects of starvation can treat and cure epilepsy just as, and in some cases more, effectively than pharmacological treatments. This dietary treatment has been around since the 1920s, but extended fasting has long been known to be effective as a treatment for seizures—it is mentioned both in the Bible and in writings from the Middle Ages.

Of course, starvation is not a sustainable cure in the long run, which is why doctors developed a diet that can safely mimic the metabolic effects of starvation. While normally our bodies burn glucose for energy, starving bodies burn fat which the metabolism breaks down into “ketone bodies” for energy. Normally, brain metabolism depends solely on glucose but, under conditions of carbohydrate restriction, it can use “ketone bodies” to supplement glucose as a metabolic substrate. In 1921, Dr. R. M. Wilder developed the modern ketogenic diet, a high-fat, low-carbohydrated, and minimal protein diet where nearly 90 percent of the calories are fat-based.

If such an effective treatment for epilepsy has been around for so long, why do so few people know it exists, and why is it still a mystery as to how it actually works?

Dr. Douglas Eagles, a professor in Georgetown’s Department of Biology, explains that the development of the highly effective anticonvulsant medications such as phenytoin and Depakote (valproic acid) in the 1930s caused doctors to put aside the diet-based therapy for many decades. The use and study of the ketogenic diet slowly began to re-emerge in the 1980s, perhaps most rigorously at Johns Hopkins.

The ketogenic diet received enormous public exposure when Hollywood director Jim Abrahams (Airplane, Hot Shots, Naked Gun) directed First Do No Harm in 1997, starring Meryl Streep. The movie dramatized Abrahams’ family’s personal struggle with epilepsy.

“Abrahams and his wife witnessed their young son Charlie’s full remission from nearly constant seizures after they brought their son to the ketogenic diet treatment center at Johns Hopkins, which they had discovered as a last resort, since Charlie wasn’t responding to other therapies,” says Dr. Eagles. Abrahams made the movie to bring greater awareness of this little-known therapy that saved his son’s life.

Dr. Eagles and his student researchers are among those attempting to understand how the ketogenic diet works to treat epilepsy. Dr. Eagles’ curiosity was piqued in the mid-’90s when an epileptic student of his brought the treatment to his attention. Driven to learn more about the treatment, Dr. Eagles visited the pediatric epilepsy clinic at Johns Hopkins. There, he spoke with clinicians using the diet to treat children with seizures refractory to drug treatment and had an opportunity to observe a range of outcomes following dietary therapy. Some were virtually cured, some were much improved and some were helped very little by the diet. Not only is the diet often effective, but its effects can be seen in a matter of days and, in the best of cases, persist for years, even after weaning from the ketogenic diet.

“One time, when a mother was being interviewed during her daughter’s successful treatment, and was asked whether her daughter was different from when she arrived at the facility, all she could do was cry,” says Dr. Eagles. “When they first arrived, their daughter was limp in their arms from all the drugs being used to combat the seizures, and now she was talking and playing like a normal child. The mother had gotten her daughter back, and weeks prior to that, she wasn’t sure how long her daughter would live.”

Currently, Dr. Eagles and his students are using the ketogenic diet as an investigative tool in their lab. Working on a hypothesis linking metabolism and epilepsy, Dr. Eagles and his researchers are looking at links between ketone bodies, metabolism, energy, and excitability in the brain.

“We are interested in understanding mechanisms of seizure generation and in seizure protection,” says Dr. Eagles. “A major tool in this investigation is the use of calorie restriction, high fat diets, or both to alter seizure threshold.”

The Eagles lab uses young white male rats as its subjects, starting them on ketogenic and non-ketogenic diets 15 days after weaning. Dr. Eagles then tests and records the rats’ seizure thresholds, attempting to induce seizures using electroshock and or injections of PTZ (pentylenetetrazole), a convulsant drug. All procedures in the lab are in accordance with the Georgetown University Animal Care and Use Committee standards.

“The theory,” explains Nik Kappy, a Georgetown College undergraduate working in Dr. Eagles’ lab, “is that the ketones produced in the body as a result of the ketogenic diet increase the release of the neurotransmitter gamma aminobutyric acid (GABA) in the brain, causing nerve cell stabilization.”

Dr. Eagles’ team is trying to understand fundamental questions about how the ketogenic diet works, such as, does it increase or decrease the brain’s energy supply? This question leads back into questions about epilepsy itself, which is a complicated illness that is still being researched.

“The question is, why do these neurons generate this activity in the first place?” says Dr. Eagles. “The hypothesis driving our investigations is that brain energy utilization has a general role in determining seizure threshold and severity.”

While a variety of factors influence the particular characteristics of each of the many epileptic syndromes, “the broad effectiveness of dietary manipulation, particularly caloric restriction, suggests that metabolism and energy play a critical role,” explains Dr. Eagles.

The work of Dr. Eagles and his students contributes to a vital pool of research on epilepsy and its treatments, building a more effective and thorough knowledge not only of the illness’s neurobiological underpinnings, but about neurobiology as a larger field of study.

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