12:11 p.m. Friday, February 26, 2010Shawn Helbig can only read small words but knows every line of “High School Musical.”
He smiles easily, but struggles to hold a conversation.
The 27-year-old lives at home and holds a part-time job at a pet store.
Shawn has Fragile X Syndrome, which is the most common inherited form of mental impairment.
But he recently started taking a caramel-colored pill every day he hopes might help him communicate better, process thoughts more smoothly and put him more at ease in the world around him.
Shawn is Emory University’s first test patient in a clinical trial for the drug originally developed for anxiety disorders. It’s a drug that could maybe, just maybe, someday help him learn to live independently, like most 20-somethings.
The pill, which currently has no name and is identified only by a number, could be the very first pill to treat the root cause of an intellectual disability.
“Before, we could never do this,” said Dr. Jeannie Visootsak, who is running the clinical trial at Emory’s Fragile X Center. “This is the first time we are looking at treatment. I never thought we’d be here today. It’s amazing.”
Emory’s drug trial will ultimately enroll a total of 60 patients. In Atlanta, the total number will be about 15. In addition to Shawn, six more test patients in Atlanta have recently started taking the pill.
If the trials, being conducted by F. Hoffman-La Roche pharmaceutical company, are successful it could have far-reaching implications for other drug treatments — for disabilities long considered permanent and untreatable.
Up until now, doctors could only prescribe medicine for some of the symptoms of Fragile X patients, such as hyperactivity and anxiety. But researchers believe they are now on the cusp of being able to prescribe a drug to address the molecular basis of the disease.
Besides Roche’s clinical trial, a small number of other clinical trials are under way, including one in its early stages by Massachusetts-based Seaside Therapeutics and another one by Swiss drug maker Novartis AG in Europe. Their drugs might have a similar effect on Fragile X patients, but because of the competitive nature of drug development, it’s not clear who might be the first one to bring such a drug to market.
Researchers don’t expect the drug Shawn is taking to cure Fragile X, but they say it might alter the brain chemistry of people with the syndrome enough to improve the mental abilities of children and adults who have been labeled intellectually disabled or mentally retarded since childhood.
Helping a child with Fragile X have fewer tantrums and be less anxious and sensitive to sounds can let the child better concentrate and focus, and ultimately live a more normal life.
It’s a moment Emory has been building toward since 1991, when Dr. Stephen Warren, chairman of human genetics at Emory University’s School of Medicine, led a team of researchers who identified the gene on the X chromosome responsible for Fragile X.
Since then, researchers have made more breakthroughs in neuroscience to better understand how Fragile X affects the brain — and what could be done to reverse it.
Once a week Shawn, who lives at home with his parents and younger brother in Johns Creek, spends up to eight hours at the center, getting blood drawn and undergoing a physical exam to monitor the effects of the drug.
Shawn, who is considered highly functioning, hopes to see changes within himself.
“I want to be different,” he said.
Clad in jeans and pink oxfords, he pauses. His bashful smile disappears. His brown eyes turn serious.
“Maybe it will make me smarter,” he says.
His mother, Sandy Britt, holding back tears, also has big dreams for Shawn.
“This pill gives every parent hope,” she said. “If it’s 5 years or 10 years or 2 years, you can see there’s a light at the end of the tunnel.”
Others don’t understand
By the time Shawn was 2, his mother knew something wasn’t right.
His speech was delayed and he was prone to outbursts over little things like his wooden blocks tipping over. By kindergarten, Shawn still had trouble writing his name.
His teachers and day care workers dismissed the signs and told Britt she just needed to discipline her son. But when Shawn was 7, she took him to see a developmental pediatrician who diagnosed the boy with Fragile X.
As a child and teenager, Shawn took speech and language therapy. He took special education classes and work-study programs. He graduated from high school in 2001.
Britt said she has encouraged him to be independent. She lets him keep money in his wallet. He has a house key allowing to him be home for a few hours without supervision.
But Shawn lives a life of routine: Every morning, he gets up at 6 a.m. and eats a toasted bagel. At 1 p.m., he watches “All My Children.” At night, he shuts his door to his bedroom and sings along to the music of “High School Musical,” a movie he’s watched hundreds of times.
Britt said her son is a “big teddy bear,” and she often uses the word “sweet” to describe him.
Over the years, Shawn’s outbursts have become less frequent, but they can be intense. About 9 years ago while on a family vacation in Key West, Shawn fell apart during a star-gazing cruise. Britt said her son was eager to get on the yacht, but 10 minutes into the trip the darkness, the crowd and unfamiliar noises on the boat became too much. He screamed and cried, collapsed onto the floor and curled up in a fetal position.
“There were the stares and the looks and people saying things like ‘he must be drunk.’ Others were yelling, ‘I want my money back!’ ” she said. “You just never know when these things might happen.”
She devised a method to answer strangers’ stares. She carries in her purse laminated cards with a pale blue X and information about Fragile X.
“When you see Sean, you don’t think there’s anything wrong and then when people get a response that is not age- appropriate, they give him this look like, ‘What is wrong with you’ and then they look at me, like ‘And what is wrong with you?’ ” Britt said. “So I just give people this card. It’s just easier that way.”
Drugs show promise
About 100,000 Americans have Fragile X syndrome.
People with Fragile X lack an important protein known as “FMRP” that acts to regulate other important proteins in the brain. Without FMRP, which puts the brakes on other brain proteins, there’s an over-stimulation of brain connections that can impair brain development.
About four years ago, Luca Santarelli, vice president and global head of neuroscience at Roche, realized an experimental drug tested on anxiety disorders might also have an application for the over-production of proteins in Fragile X brains. Dr. Randi Hagerman, who directs the MIND Institute at the University of California, Davis, and is involved in multiple clinical trials for Fragile X medications, believes the experimental drugs are showing promise with improving language, eye contact and behavior.
“In the bigger picture, I think Fragile X will be one of the first disorders associated with intellectual disability with significant reversal,” she said.
She believes treating Fragile X could provide enormous opportunities to treat autism, which is closely related. While a third of people with Fragile X are also autistic, only between 2 and 6 percent of people with autism also have Fragile X.
Even with signs of promise, developing a treatment is a daunting proposition. Most experimental treatments fail to make it through the three phases of clinical testing needed before they can get FDA approval for use in the public. Still, with so many leaps in grasping how Fragile X affects the brain, Warren believes real help is within reach.
“You can look at these kids and you get this impression they know what’s going on and they are having a tough time expressing themselves and they have social anxiety,” he said. “There’s a light-behind-the-eyes sort of thing.”
Pill represents hope
Britt believes that since he began the drug trial, her son has become more communicative and his words less slurred and he makes better eye contact. But she admits the changes could just be her own wishful thinking. For his part, Shawn said he doesn’t have as much trouble talking.
Dr. Stephen Warren of Emory said it’s premature to make any conclusions: the study is double-blinded, which means only some of the participants are getting the experimental drug while others are simply given a placebo, and not even the doctors know who’s getting what.
With the trial in its fourth week, Shawn shows up with violets for Visootsak, who asks everyone to call her by her first name.
“Ah, how sweet. You make me smile,” said Visootsak. “My connection to Fragile X is patients like Shawn.”
Visootsak spends a lot of time talking to Shawn. She listens intently to him wistfully talk about his high school days, going to the prom in a limousine, his mom crying at his graduation.
Visootsak said she would love to see Shawn live independently someday.
For Britt, this pill represents the hope she’s clung to for decades.
And while she still carries those laminated cards in her purse, she clutches hope that there may be a day she can leave them behind.
“It may unlock what’s stuck in their minds,” she said. “Imagine having something locked up in your brain and you can’t get it out. Imagine the frustration that is there. ... You’ve just got to have hope because if you don’t have hope, you’ll live a downer of a life.”
----------------
About Fragile X
What is Fragile X syndrome?
Fragile X syndrome is the most common cause of inherited mental retardation, affecting about 1 in 4,000 boys and 1 in 8,000 girls. It can cause a range of mental impairment — from mild learning disabilities to severe intellectual disability. Physical features of Fragile X that may or may not be present include long ears, faces and jaws. Many children with Fragile X have behavioral challenges. Boys are more likely than girls to have trouble paying attention or being aggressive. Girls may be shy around new people.
What causes Fragile X?
It is an inherited mutation of a gene (FMR1), found on the x-chromosome. While the mutation is passed from parents to children, parents may have the mutation but not have Fragile X themselves. The gene normally makes a protein needed for brain development, but the mutation causes a person to make less or none of the protein.
Why are boys more affected than girls?
Boys are generally more affected than girls because girls have two X chromosomes and the one without the mutation can partially compensate for the non-functioning one.
SOURCE: University of Michigan Health System, National Institutes of Health
