Available in print and downloadable PDF.

Issue 22013

Bench-to-Bedside

Smiles were few, and the thought of having family pets was unfathomable for the Maxwells when Aidan was on his previous anti-seizure medication.

Sandra Bretting

Imagine wheeling your 2-year-old son around Disneyland in his stroller, listening while his cousins squeal with delight at every passing sight and sound. Suddenly, one of the Disney characters appears before your group, all buck teeth, silly grin and floppy ears.

“The responses were just crazy-different,” said Lisa Maxwell, whose son sat in his stroller that day. “Goofy came up to us and the other kids were so excited to see him — he’s a 6-foot dog, after all — but Aidan didn’t even look up.”

Aidan was on anti-seizure medicine that left him, in his mother’s words, “catatonic.” Diagnosed at birth with a rare multi-systemic disease called tuberous sclerosis complex (TSC), Aidan began suffering epileptic seizures when he was 2 years old.

The seizures required medicine that turned him from a happy, playful child into one who couldn’t even communicate.

“I had little hope for him,” Maxwell said. “Verbally, cognitively … he was haywire. I had the feeling he wasn’t going to be able to achieve much in life and that his social skills would be so bad he would never have any friends.”

Aidan’s problems worsened by the time he turned 6. Now taking a different medicine, he became so aggressive in kindergarten that his teacher had no choice but to send home weekly progress reports that were marred with bright-red marks.

A New Source of Hope

The fall of 2010 marked a turning point for Aidan and his family, however. Behind the scenes in the Cain Foundation Laboratories at the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital, epilepsy researchers had been studying the brain pathways of animals with Aidan’s type of illness.

NRI Co-Director John Swann, Ph.D., had been studying tissue taken from children with intractable epilepsy for whom surgery was the only option. Then, he and his team replicated in mice the overactive brain pathway they found in the children’s tissue samples. The mice had seizures, but Swann and his team found that certain medicines affecting the overactive pathways stopped the seizures.

“Ours is a unique relationship in the field of pediatric neuroscience, and it creates a dynamic that doesn’t exist in many places,” Swann said. It allows us to study neurological diseases collaboratively between lab and clinic and move intervention therapies forward faster.”

Over the course of this research, Swann had been sharing his information and findings with staff physicians at Texas Children’s. This coordination was made possible through a unique collaboration between researchers at the NRI and clinicians at Texas Children’s that allows researchers to share their findings with doctors who are actively engaged in treating patients with diseases like epilepsy.

“Ours is a unique relationship in the field of pediatric neuroscience, and it creates a dynamic that doesn’t exist in many places,” Swann said. It allows us to study neurological diseases collaboratively between lab and clinic and move intervention therapies forward faster.”

Meanwhile, researchers at Cincinnati Children’s Hospital were engaged in studies of a medicine called everolimus. Originally developed to help prevent the rejection of transplanted organs, everolimus also seemed in studies to reduce the growth of brain and kidney tumors such as those associated with TSC. In the course of this research, physicians at Cincinnati Children’s noted that everolimus also seemed to have a positive effect on seizure activity in patients with TSC — bringing the study to the attention of physicians at Texas Children’s.

“It was work that had been going on independently, until it all coalesced,” said Angus Wilfong, M.D., director of the comprehensive epilepsy program at Texas Children’s. In August 2012, the two hospitals linked up to conduct a drug trial to study the effect of everolimus on epileptic seizure activity in patients with TSC. Ten patients were enrolled in the study at each hospital, and Aidan was among them.

“Of the 20 patients, 17 had dramatic improvements in their epilepsy,” Wilfong said. “Most of the time, when you’re talking about a new drug for epilepsy, if two or three people out of 10 have a good response, that’s considered really, really good. It was dramatically more effective than any other medicine that had been used.”

What also encourages researchers is that this medicine may potentially repair damage already done by the disease.

“We have more than 30 drugs that are referred to as ‘anti-epilepsy drugs,’ but they’re not really anti-epilepsy drugs; they’re anti-seizure drugs,” Wilfong said. “They don’t make the epilepsy better. Because this medicine changes the brain’s pathways and helps the brain re-regulate cell growth and cell connections, we strongly believe that it can help the brain fix itself.”

Remarkable Transformation

Maxwell said that once Aidan began taking the drug, the change in her son was nothing short of miraculous.

“We saw profound differences in him in just six months,” said Maxwell. “Not only his seizures, but also his cognitive abilities, his communication abilities, his social abilities … all of those things started changing.”

Bench-to-Bedside

Aidan has been seizure-free since he began his new medication, everolimus. He now can attend regular classes at school and enjoy many of the same activities as other boys his age, like playing video games and riding his scooter.

And Maxwell wasn’t the only one to notice a difference.

“His teacher said she’s never seen a medicine do so much for a child,” Maxwell said.

Seeing Aidan’s progress was just as much of a reward for Swann.

“I’ve been studying childhood epilepsy as a researcher for 30 years, so to finally meet a child my work has helped was incredible,” Swann said. “It really was a moment when all of that work — when all of that effort — really paid off.”

Because of the study’s success, the medicine’s manufacturer has launched an international drug trial that will enroll 500 patients in some 70 countries. That study launched in June, and Texas Children’s already has enrolled 20 patients in it.

For the Maxwells, everolimus has meant the difference between Aidan falling further and further behind his peers — maybe never to catch up — and his being able to concentrate and learn again. Perhaps best of all, his family said that his social skills have drastically improved.

“Remember how I said I was worried that Aidan would never have friends?” Maxwell said. “This past year, two little boys actually began to play with him and ask to sit next to him in school. They didn’t feel sorry for him because he had this disorder, and they weren’t just trying to be nice. They really wanted to be his friends.”