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Cancer drug dramatically reduces epileptic seizures


Houston_Chronicl

07-18-13

July 17--Houston researchers have dramatically reduced the occurrence of seizures in a small group of children with epilepsy, using an existing cancer drug they think may be able to treat up to 1.5 million people with intractable forms of the disease.

In a new study, Texas Children's neurologists found that children with a rare, severe type of epilepsy received great benefit from Everolimus, a smart drug approved for the treatment of kidney and brain tumors. The drug targets faulty signaling in the brain that causes uncontrolled cell growth.

"The exciting thing is that this is anti-epilepsy therapy, not just anti-seizure therapy," said Dr. Angus Wilfong, the director of the comprehensive epilepsy program at Texas Children's and one of the study's principal investigators. "For the first time, we have a drug that addresses the underlying cause of seizures, changing the brain and the way it sends and receives disease-causing signals."

The study, now online in the journal Annals of Neurology, is important even though it only enrolled 20 children because the benefits were so "life changing" for most of them, Wilfong said. He added that the difference in children before and after treatment was "like night and day."

Wilfong will lead the Texas Children's arm of an international trial that will test Everolimus on patients whose type of epilepsy is more common but still characterized by the same signaling problems. The trial, already started in Europe, aims to enroll 500 patients at as many as 70 sites, including some in Asia and Latin America.

The small study, conducted at Texas Children's and Cincinnati Children's hospitals, tested Everolimus on patients with tuberous sclerosis complex, a genetic disorder that causes non-malignant tumors to form in different organs. Those in the brain affect signaling in a key molecular pathway and cause seizures.

The condition is found in one in 6,000 births and accounts for between 1 and 2 percent of the nation's 3 million cases of epilepsy. But Wilfong said the same pathway signaling problems occur in 30 percent to 50 percent of cases.

Children in the study received Everolimus for 12 weeks, during which time their symptoms were monitored. Seventeen of the 20 participants experienced an average 72 percent reduction in their overall seizure activity -- four became completely seizure free and the others reported seizures that were milder, shorter and less frequent.

Among the successes was Aidan Maxwell, a 9-year-old boy who, diagnosed at birth, began suffering seizures at 23 months. By the time he was 6, his frequent, severe seizures caused autistic-like symptoms -- developmental delay, a lack of communication, tantrums -- that his parents assumed meant he'd never be a functioning adult.

About that time, Aidan began taking Everolimus. Though he's not completely seizure-free and his development lags behind, he is, for the first time, relatively healthy and independent.

"I thank God for that drug," says Lisa Maxwell, his mother. "I don't know who my son would be today without it. He's now like any other kid, playing and laughing."

The drug is not without downsides. It costs several thousand dollars a month and appears likely to need to be continued through one's life since its withdrawal would result in a resumption of the brain's faulty signaling -- though Wilfong thinks early use might prevent the growths that cause the condition.

Though Everolimus is a mild immunosuppressant, Wilfong said side effects were minimal. Short-lived mouth ulcers were the most common side effect.

Janice Buelow, vice president of programs and research for the Epilepsy Foundation, called the study "a good, promising start," noting the impressive results occurred with very difficult-to-treat cases.

She said she looks forward to the larger trial attempting to replicate the results.

Wilfong, who got the idea to conduct the study after noticing the decline in seizures among tuberous sclerosis complex patients treated with Everolimus for tumor growth, said there's a buzz over the potential new application of the drug.

"I haven't been to a conference recently where this therapy hasn't been the subject of discussion," said Wilfong, also a Baylor professor of pediatrics and neurology. "I think this is the dawn of a new era in seizure treatment."

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(c)2013 the Houston Chronicle

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Copyright Houston_Chronicl 2013

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