discovers an epilepsy therapy
diet that simply cuts back on calories may hold an answer to controlling
epilepsy, according to research done by a Boston College undergraduate
and published in the medical journal Epilepsia. The study
is the work of Amanda Greene '00, and was begun while she was a
Epilepsy is a chronic disorder marked by disturbances in the brain's
normal electrical functions. These sudden and intense bursts of
electricity, or seizures, affect a person's awareness, movement,
or sensation. About 40 million people worldwide have epilepsy. Their
seizures can be controlled, but there is no cure. The most common
treatment is medication that suppresses the brain's tendency to
produce excess electrical discharges. When that doesn't work, the
involved part of the brain may be surgically removed. Another option,
popular to varying degrees in this country since the 1920s, is the
ketogenic diet, which consists mainly of fats with very little protein
or carbohydrates. The diet is moderately successful in children,
but has unpleasant digestive side effects.
In 1998, Dr. Mariana Todorova, who is director of biological labs
at BC, was researching the effectiveness of the ketogenic diet in
a breed of seizure-prone mice, developed for epilepsy studies. She
was working with biology professor Thomas Seyfried, who also was
looking at diet therapies in mice on another project--exploring the
potential impact of diet on brain cancer. His focus was on the effects
of calorie reduction.
When junior Amanda Greene appeared at the lab in Higgins Hall asking
for the chance to do some research, Todorova and Seyfried decided
to see whether caloric restriction would do anything for the seizures
that define epilepsy.
"It was a shot in the dark--we didn't have a clear idea what would
happen," Seyfried says. "But, we figured, what did we have to lose?"
For a semester, Greene shadowed Todorova, learning to handle the
mice--how to pick them up by their tails to induce the stress that
helps activate seizures--and to document data. To hone her understanding
of the statistical methods required for her project, she turned
to Richard McGowan, SJ, at the Carroll School of Management. In
her senior year, as a scholar of the College, Greene pursued the
epilepsy experiment as her independent project.
For the experiment, Greene fed juvenile mice the same nutritious
mouse chow that she fed to a comparable control group, only 15 percent
less. She also fed two adult groups 15 percent and 30 percent less
than their counterparts in an adult control group. After processing
the numbers, Greene found that the reduced-calorie diets had cut
the incidence of seizures in the juvenile and the adult mice.
In the young animals, the reduced diet delayed the onset of epilepsy.
Moreover, Greene's dieting juveniles had fewer seizures than did
young mice elsewhere in the lab who were on the ketogenic diet.
The adult mice benefited less, seeming to require larger calorie
cuts to achieve smaller gains. But, since adult mice obtain no benefit
from the ketogenic diet, even a modest improvement was significant.
"The data is really striking," Seyfried says, and he plans to find
another student to test the idea further. "We think we've defined
a new therapy with no adverse effects."
Equally significant, Greene found out why the diet works, and why
the ketogenic diet also helps prevent seizures.
The ketogenic diet is named for ketones, substances formed by the
body when it breaks down fat. Scientists have long known that large
amounts of ketones in the blood--typically present when a person
is starving and has literally to live off fat--are associated with
a decrease in seizures. The idea behind the ketogenic diet is that
eating large quantities of fat produces more ketones and will reduce
Greene noted in her mice that a lower-calorie diet produced an increase
in ketones, but also resulted in a decrease in the amount of glucose
in the blood, which, she theorized, explains why the body turned
to metabolizing fat, or ketone bodies, in the first place. The brain
usually metabolizes glucose for energy, but when the supply of glucose
is low, it resorts to metabolizing ketone bodies. The energy gained
is sufficient to meet normal needs, Greene hypothesized, but not
powerful enough to support seizures.
"What Mandy found was that ketones were a red herring, taking
attention away from the really important issue, which was glucose,"
Seyfried says. "The ketones are the effect of reducing glucose,
but glucose is the major metabolite regulating the seizures. It's
a conceptually important study."
Greene's paper, which credits Todorova, McGowan, and Seyfried as
coauthors, appeared in Epilepsia last November. According
to the journal's editor, Timothy A. Pedley, publication by an undergraduate
is a rarity.
Gregory Holmes, a professor of neurology at Harvard Medical School,
describes Greene's study as "provocative." Says Holmes, "It's a
very clever idea and a nice model. It indicates that some of the
torturing things we do to kids [to treat seizures] may not be necessary."
Holmes cautions that further research will be needed to make sure
that calorie cuts won't impair learning, but he sees an encouraging
sign in Greene's findings that lab mice on the lower-calorie diet
appear more alert and active than those getting full feed.
Greene, now 24, is doing neurology research at Boston's Children's
Hospital as part of a team studying periventricular leukomalacia,
a condition underlying cerebral palsy in premature infants. She's
applying to medical school and wants to be a pediatric neurologist.
Seltz is a writer based in Hingham, Massachusetts
Photo: Greene in the BC lab where she made her finding