Deciphering My Myeloma Lab Results

fragile x syndrome genetics :: Article Creator

Fragile X Held Him Back. An Experimental Drug Is Helping Him Break Free

For 22 years, Jason Mazzola's life was defined by Fragile X, a genetic condition that often causes autism and intellectual disability.

Jason, who is 24 now, needed constant supervision. He had disabling anxiety, and struggled to answer even simple questions.

All that began to change when he started taking an experimental drug called zatolmilast in May of 2023.

"It helps me focus a lot, helps me get more confident, more educated," Jason says.

His mother, Lizzie Mazzola, credits zatolmilast with transforming her son.

"I have a different child in my house," she says. "He gets himself to work, he walks downtown, gets his haircut, gets lunch. He wouldn't have done any of that before."

Other parents of children with Fragile X are also reporting big changes with zatolmilast.

Those anecdotes are supported by data.

A 2021 study of 30 adult male participants with Fragile X found that taking zatolmilast for 12 weeks improved performance on a range of memory and language measures.

Now, two larger studies are underway that will determine whether zatolmilast becomes the first drug approved by the Food and Drug Administration to treat Fragile X.

Brain, interrupted

Mazzola realized early on that Jason was falling behind.

Jodi Hilton for NPR/Jodi Hilton for NPR /

August 22, 2024, Natick, MA. Photos of the twins Jason and Jessica as children. Both were born with Fragile X syndrome.

"He could hardly talk by three," she says. "At four he started to put some words together, but really wasn't talking in sentences."

Genetic tests revealed the cause: Fragile X.

The inherited condition affects the X chromosome, making one segment appear fragile or broken. This anomaly blocks production of a protein that's important to brain development.

The result can be autism, ADHD, anxiety, sensory sensitivity, and a range of intellectual disabilities.

For Jason, many of these symptoms were severe. Like many people with Fragile X, his IQ was in the 40s, and he was often paralyzed by anxiety.

Jason's twin sister, Jessica, also has Fragile X, but the symptoms are absent or much milder.

That's often true of females with the condition. They typically benefit from having two X chromosomes, one of which is unaffected.

So while Jessica went on to college, Jason was still barely able to converse, even with his parents.

"He's always wanted to be social. He's a friendly person," Mazzola says. "But because his communication skills were so impaired, he struggled to put his thoughts into words."

Jodi Hilton for NPR/Jodi Hilton for NPR /

August 22, 2024, Natick, MA. Jason Mazzola at home with his twin sister Jessica and dog Marley. Repurposing an Alzheimer's drug

By the time Jason was a teenager, scientists had begun studying the link between Fragile X and an enzyme that plays a role in memory and cognitive impairment.

Much of the funding for this research came from the FRAXA Research Foundation, a group founded by the parents of a child with Fragile X.

FRAXA-funded researchers knew there were drugs that could tweak the enzyme in a way that might help a Fragile X brain work better. But the drugs all had side effects that made them unsuitable for people.

Then one day FRAXA got a call from Tetra Therapeutics, a small drug company in Michigan.

"They had this drug in clinical trials for Alzheimer's disease," recalls Dr. Michael Tranfaglia, FRAXA's co-founder and medical director. "They wanted to explore the possibility of using their drug in Fragile X."

That made sense because the drug targeted the same enzyme FRAXA had been studying and it didn't seem to cause the side effects that had ruled out similar drugs.

The next stop for Tetra was Dr. Elizabeth Berry-Kravis, a professor at RUSH University Medical Center in Chicago. Berry-Kravis had been studying the way Fragile X affects brain development for nearly three decades, and was receiving funding from FRAXA.

So she got a visit from a Tetra executive.

"Mark Gurney, who was the head of the company at the time, came to my office and said, 'Hey, you've got this mechanism that you've been waiting for a drug for for 28 years, and we've got a drug,' " Berry-Kravis recalls.

The drug was zatolmilast.

Jodi Hilton for NPR/Jodi Hilton for NPR /

August 22, 2024, Natick, MA. Jason Mazzola works as a dishwasher at The Residence at Natick South. Jason unbound

A flurry of research showed that zatolmilast worked in fruit flies and mice with Fragile X. The 2021 study of 30 male adults extended the promising results to people.

"We saw an improvement in their memory and their vocabulary and their ability to read," Berry-Kravis says.

The next step was to have Berry-Kravis oversee a pair of larger studies – one in males from 9 to 17, the other in males from 18 to 45. The studies got underway in 2022, with funding from the Japanese drug company Shionogi, which had acquired Tetra.

Mazzola decided to enroll her son, Jason, who was now in his 20s. She was optimistic about zatolmilast, despite having witnessed the failure of other promising drugs for Fragile X

"It just seemed different," she says. "It was affecting their cognition and IQ scores."

At first, Mazzola and her husband didn't know if their son was getting zatolmilast or a placebo.

Within a few weeks, though, Jason did something remarkable: He walked into his father's home office and started a conversation.

"My husband said, 'He has to be on the drug. He's never done that,' " Mazzola says.

Jason is still taking the drug, and still improving, Mazzola says. He has a job washing dishes at a local assisted living facility. He helps his mom coach high school field hockey and lacrosse.

Jason himself offers perhaps the most compelling evidence that the drug is working.

Jodi Hilton for NPR/Jodi Hilton for NPR /

August 22, 2024, Natick, MA. Jason Mazzola getting his haircut by Jose Nieves at Title City.

At his home in a Boston suburb, the young man who was once paralyzed by simple questions agrees to an interview.

When I ask Jason to tell me something about himself, he's got an answer:

"I play a lot of sports like hockey, basketball and golf," he says. "Golf is really fun because I play with my dad."

"You good off the tee with the driver?" I ask.

"Yeah, the driver," he says, "and the six iron and the seven and the putter."

A scientific verdict on the drug will come when the study is completed, probably in 2025.

There's Evidence Fragile X Symptoms Can Be Reduced With An Experimental Drug