Fragile X: Drug trial offers hope to patients with mental disability caused by genetic mutation

Tim Seward heads out of his humble Burbank home, yelling back to his mom, who has just settled into a chair in their family room.

"See you later," he says.

Moments before, his mom runs down a checklist of questions.

"What's in the cooler?"


"Who are they for?"


"What color is Cruise?"


He then excitedly leaves for the horse stables.

In many ways, Mary Seward says, she's living with Peter Pan.

Her 21-year-old son was born with Fragile X syndrome, a genetic mutation of the X chromosome that causes intellectual disability, according to the National Institutes of Health.

"He's still got the heart and soul of a 5- or 6-year-old," Seward says. "He's just so sweet and so much fun. He has a hard time doing things, but you don't mind helping him."

Though there's no cure for Fragile X, engaged conversations like the one above are becoming more frequent and in-depth thanks to a breakthrough study Tim is involved in at Miller Children's Hospital in Long Beach.

The trial is for a drug called arbaclofen, which targets the social withdrawal or social avoidance behaviors that are a key issue with Fragile X, says Dr. Gary Feldman, the medical director at the Stramski Children's Developmental Center at Miller Children's Hospital.

Feldman is handling the local trials for arbaclofen and another drug called mGlu5 receptor antagonist, which also aims to curb the social avoidance behaviors associated with Fragile X.

Tim began the six-week double-blind portion of the study in fall 2011 and the family still doesn't know if he was on the placebo. But in April 2012, he started a trial with the actual drug.

Since then, Tim's mother and Feldman have seen remarkable changes, they say.

"Since he has been on the open label arbaclofen study his gaze avoidance has improved. Tim's social communication has improved - he is starting to greet people spontaneously and introduce himself by name," Feldman says.

"Speech therapist reports a big difference in his reading and his vocabulary has increased," the doctor says. "When I saw him earlier this month, he was noted to speak much more richly and he was verbally more animated."

Feldman says Tim was able to talk about a movie he had watched and to point out the characters. It was also noted that he has taken more of an interest in looking at and trying to read books.

Tim's parents first noticed arbaclofen was working in June when they threw a party at their home and Tim introduced himself to one of their guests. It was the first time he had ever done that.

Though Tim has been on a variety of medications since age 4, Seward says this is the first drug that has targeted the specific gene linked to Fragile X syndrome, the Fragile X Mental Retardation 1 gene, or FRM1.

Because of the genetic abnormality, people with Fragile X syndrome do not produce a protein called Fragile X Mental Retardation Protein (FMRP), which regulates and controls the production of proteins that govern how nerves are formed, says Feldman.

"So the way these drugs work, particularly this one, is it's designed to stimulate the release of a controlling chemical that will prevent this runaway production of proteins," Feldman says.

"I would say more than 50 percent of the cases on the open label we have seen some significant improvements and it's of the more social context - initiating more social contact, making better eye contact, being more verbal, speaking more and a decrease in anxiety."

The drug is also being used in a study for children with autism, as they have similar symptoms as people with Fragile X.

But the two may be even more closely related.

About a third of those diagnosed with Fragile X also have a clinical diagnosis of autism, making it the most common known genetic cause of autism, according to the National Fragile X Foundation. And for others who do not have the clinical diagnosis, they still most likely have autistic-like behaviors.

The study of arbaclofen on children with autism is also showing great promise on the same social avoidance behaviors, says Feldman.

Fragile X is rare compared to autism, but the link between the two has helped generate funding for Fragile X research, says Seward, who is treasurer of the Fragile X Association of Southern California.

Because Fragile X is a single-gene defect that causes autistic-like tendencies - whereas the causes of autism are still relatively unknown - the thought is if researchers can find a way to alleviate those symptoms in Fragile X patients they also can rid austic children of the same symptoms, says Seward.

So far, Feldman says, the drugs are very promising for both categories of patients.

"I think they're going to make a big difference in the quality of life for these kids," Feldman says. "Bottom line is I'm very excited. It's exciting to be involved in something you can see is going to be very helpful."

As for Seward, she says this is the most exciting breakthrough she's seen, comparing it to when researchers discovered insulin for diabetes.

Though she knows there will be no cure for her son, all she wants is for him to have a better quality of life.

"It's been a long journey but we really enjoy him," Seward says. "They really tug at your heartstrings once you get to know them, but they don't allow everyone into their world."

Stephanie Cary 310-540-5511, Ext. 6630

Follow Stephanie Cary on Twitter: @stephiecary