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Matthew's liberation

Seaside at forefront of new approach to Fragile X

By Karen Weintraub
Globe Correspondent / August 23, 2010

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It was the week the medication didn’t work that convinced Melissa Zolecki. She thinks her son Matthew got a bottle of inactive dummy pills that week by accident. And the change in his behavior was striking.

He was back to banging his head against the wall. He struggled to concentrate again at school. Then, there was the epic temper tantrum at Costco, normally one of his favorite places. Even the temptation of a hot dog didn’t help.

Matthew, 9, was out of control in a way he hadn’t been since starting an experimental drug eight months earlier.

Matthew has Fragile X, a rare genetic disorder that leaves 1 in 4,000 boys and 1 in 8,000 girls with intellectual deficits, severe anxiety, and behavioral problems often diagnosed as autism. There is no cure. The only treatment for Fragile X, as with autism, has been extensive behavioral therapy and drugs developed for other purposes such as schizophrenia, depression, and panic attacks.

Now, Matthew is one of the first patients on one of the first medications ever developed specifically to address the causes of an autism-like disorder. And — at least for him — it seems to be working.

“Our quality of life is just better,’’ said Zolecki. That week “made me realize I did not want to go back to the life we had before.’’

Seaside Therapeutics, a Cambridge start-up, is studying the drug, called STX209, in 60 children across the country. The company said the second round of research will soon be reviewed by the federal government, and if it meets standards for safety and effectiveness, more children with Fragile X will be given the drug for a larger trial.

If all goes well, it will also be tested in children with autism, a set of behavioral and social problems that has proved extremely difficult to treat even as the number of children with it has seemed to explode. Almost 1 in every 100 children is now diagnosed with the disorder.

Large pharmaceutical companies, including Pfizer, Roche and Novartis, have also become enthusiastic about developing autism drugs, searching for new compounds as well as looking on their shelves to see whether drugs they developed for other purposes might help with autism.

“The science is mature enough now that the pharmaceutical companies are ready to engage,’’ according to Geraldine Dawson, chief science officer of Autism Speaks, the nation’s largest autism science and advocacy organization. “With those resources, I think we’ll see the process moving much more quickly. Over the next five years, we’re going to see some remarkable breakthroughs because of this new ability to treat core symptoms of autism.’’

Matthew’s medication and another drug Seaside is developing are based on the idea that Fragile X — and maybe autism — are caused by a faulty switch in the brain. The broken switch allows too many proteins to be made at the connections between brain cells, disrupting the passage of signals along brain pathways.

MIT neuroscientist Mark F. Bear, Seaside’s scientific founder, discovered this glitch back in 2002 when he was studying the single gene that is mutated in Fragile X. The runaway protein production, he realized, could explain many of the symptoms of Fragile X, including learning issues, severe anxiety, bowel problems, seizures, and repetitive behaviors like rocking, most of which overlap with autism.

“The exciting implication was that maybe Fragile X might be corrected by taking your foot off the accelerator to compensate for the lack of brakes,’’ said Bear, who is also an investigator with the Howard Hughes Medical Institute.

Over the last eight years, Bear and other scientists interested in Fragile X have learned more about this cellular process and its role in the disorder, and begun experimenting with medications they hope will correct it.

Seaside is at the forefront of drug development because of Bear’s early role in Fragile X work, and because a close friend of Bear’s found the research so compelling that he decided to contribute $60 million to the company. The money allows Seaside to operate like a well-funded university department, rather than a company hungry for cash.

Seaside has also received more than $5.5 million in federal funding for early-stage drug development.

“We have no pressure to go public or sell the company,’’ said Daniel E. Geffken, Seaside’s chief operating officer.

Seaside, whose offices overlook Memorial Drive, has kept its work quiet until recently, not wanting to be inundated by families desperate for help the company couldn’t give.

The drug Matthew is on is related to baclofen, which is commonly prescribed for muscle spasticity. Roche is conducting a clinical trial of a similar compound in adults with Fragile X, to be completed in 2012.

These drugs, even if successful, are not expected to “cure’’ Fragile X or autism. More likely is that they would address some of the major symptoms.

“We harbor the hope that this is going to be something like penicillin was for pneumonia,’’ said Randall L. Carpenter, Seaside’s cofounder, president, and chief executive, “but we realize it may be more like turning [autism] into a more manageable disease.’’

As far as Melissa Zolecki is concerned, any assistance is welcome. Matthew’s Fragile X hasn’t been cured by the medication — their lives are still “not all roses and butterflies,’’ she said. But his anxiety and social issues have been easier to handle since beginning the drug, allowing him to make real progress in school this spring. “He actually accomplished goals instead of us having to change the goals,’’ she said.

Zolecki asked Seaside to extend Matthew’s participation in the research after the initial clinical trial ended, and she has been told that he can stay on the drug for at least another year.

In March, Matthew had his first formal birthday party. It was a bowling party, like any other 9-year-old might want, with friends and a cake decorated with golf clubs.

Matthew had always been terrified by the “Happy Birthday’’ song. The family had to avoid most restaurants because he would have a terrible panic attack if someone started singing it. But on that day, his mother said, Matthew proudly listened as his friends and family sang it to him for the first time.

Karen Weintraub can be reached at karen@karenweintraub.com.

Drugs in clinical trials for Fragile X

The MIND Institute at the University of California Davis is testing an antibiotic called minocycline against a placebo in 60 children with Fragile X. The Fragile X Research Foundation of Canada is studying the benefits of the same drug in 20 teenagers and young adults.

Seaside Therapeutics is testing the drug arbaclofen , which it is calling STX209, against a placebo in 60 children and adults, to determine its safety and an appropriate dose. Some of those study participants will continue on the drug past the initial four-week trial.

Roche is testing a similar drug it is calling RO4917523 against a placebo in 60 adults with Fragile X.

Novartis recently completed testing the safety and dosing of a drug called AFQ056 against a placebo in 30 adults with Fragile X.

Stanford University researchers are testing the drug donepezil, a medication that enhances the function of the brain chemical acetylcholine. This trial includes 50 patients ages 12 to 21.

Indiana University researchers are testing the drug Riluzole, approved by the FDA for use in treating amyotrophic lateral sclerosis (ALS) in adults. This small trial will explore the drug’s impact on six adults with Fragile X. The school is also exploring the drug Aripiprazole in 12 people over age 6.

Seaside is testing one dose of a drug called STX107 against a placebo in 40 adults. The company hopes to proceed to more extensive testing of the drug this fall.

SOURCE: Clincaltrials.gov