How Far Would You Go to Save Your Little Girl?

The Duffs were determined to beat the odds. Less than a month after returning from their meeting with Li, Joceyln and John had filed the official paperwork needed to set up a nonprofit and pulled together an all-volunteer team to help with marketing, public relations, and fundraising. They initially called the organization the Talia Duff Foundation, but after some debate changed it to Cure CMT4J in hopes of raising awareness of the disease itself and widening the foundation’s appeal to potential donors. Not long after they set up the organization’s website, Jocelyn’s inbox began pinging with messages from other families who had recently received rare-disease diagnoses—including two other families whose children have CMT4J.

Until the launch of her organization’s website, there was no easy way for families battling CMT4J to find one another. Previously, patient privacy laws made it difficult for Li and other doctors to connect families, but now Li could steer patients to the Duffs’ foundation. Suddenly, John and Jocelyn didn’t feel so alone anymore. They ended up connecting with a family in Washington State with a seven-year-old boy named Ethan, who had seen Li about his CMT4J not long after Talia. They wanted to help however they could.

Before the Duffs or any of their newfound patients-in-arms could make progress toward building a cure, though, they needed to determine whether Li’s gene therapy idea was even feasible. The best way to find out was to bring a team of scientists together from around the country and put them in a hotel for a weekend to hammer out the details. It would cost $30,000 to put this mini summit together. Jocelyn got to work.

As word of the Duffs’ mission spread throughout Ipswich, a small seaside town of 13,000, friends and strangers rallied around them. A Fourth of July lemonade stand grossed $400 in an hour. Family friends, who brewed mead as a hobby, hosted a tasting and donated the proceeds to Cure CMT4J. As did a nearby yoga instructor who led sunrise classes on the shores of Crane Beach, and a neighbor who organized a night of drinks with live music and a silent auction. Even the Ipswich High School boys’ varsity lacrosse team pitched in, wearing brightly colored “curecmt4j” shoelaces that sold for $5 a pair on the night they won the state championship. “It’s one thing for us to make a commitment because we’ve got the motivation,” John says through tears, overwhelmed by the outpouring of support. “But to ask your friends and other people to do this is a big thing. They were so receptive.”

Neighbors, friends, and strangers in Ipswich have rallied around the Duff family, helping raise money in dozens of different ways, from selling Cure CMT4J shoelaces to leading sunrise yoga classes on Crane Beach. These grassroots efforts have brought in nearly $300,000.

As small sums and donations started adding up, it was time for the next phase of the plan: bringing in the experts. Jocelyn began inviting doctors and scientists to spend a weekend in Bethesda, Maryland, pulling together an Ocean’s 11–style crew of geniuses. The guest list included Cat Lutz of Maine’s Jackson Laboratory, which specializes in genetic research, and Steven Gray of the University of North Carolina, whose lab makes viral vectors capable of shuttling therapeutic payloads to cells. Also in attendance was Guy Lenk, a geneticist who works at the University of Michigan—and is among the world’s foremost experts on Talia’s illness.

For the past 10 years, Lenk has devoted himself to CMT4J, burying his nose in microscopes and petri dishes in an attempt to piece together its mysteries. A few years ago, he and his colleagues managed to breed mice with the same genetic defect, providing a new way to study the disease. When Jocelyn cold-called him one afternoon, she expected a secretary to take a message, but much to her surprise, Lenk answered the phone on the first ring. He was stunned to hear that Jocelyn’s daughter had been diagnosed with CMT4J. “I’ve talked about CMT4J at international meetings,” Lenk says, “but I’ve never met a patient with it.” And no wonder: He estimates that the odds of being born with CMT4J are roughly one in a million. But to have Down syndrome and a FIG4 mutation? “It’s very likely that Talia is the only person in the world with both,” he notes. At first, Lenk wasn’t sure how he could help. But Jocelyn’s vision and determination quickly won him over. “She’s really pushing for this treatment,” he says. “Merck isn’t pushing for it. Pfizer doesn’t care about a one-in-a-million disease.”

In September 2016, Jocelyn assembled the experts inside the Seneca Boardroom at the Marriott in Bethesda. Each person at the table had a role to play, and it wasn’t lost on any of them that the mother of a dying girl had pulled together the highest-level meeting on CMT4J ever held. “There were moments where you had to pretend that you had something in your eye,” Lenk says. “It is a terrible disease.” As the weekend progressed, everyone agreed that CMT4J looked like a promising target for gene therapy. Finally, Jocelyn thought, the puzzle pieces were falling into place.

At the same time, something else was becoming clear: No longer was this about trying to save one young girl from Ipswich. The Duffs were fighting to push forward the entire field of precision medicine. Nearly 80 percent of rare diseases are believed to have a genetic component to them, and gene therapy could potentially treat thousands of different types of ailments. “If we show it works for CMT4J,” Gray says, “we can expand it to dozens of other diseases.” Even if the treatment didn’t work, it would give researchers something to take back to the drawing board.

Medical breakthroughs, though, don’t come cheap, and Jocelyn began wondering if lemonade stands and car washes would be enough. At a minimum, Jocelyn realized, they would need to raise at least $1 million, which would get them to the point of being able to administer gene therapy to Talia, as well as to Ethan, the boy in Washington State. More-conservative estimates put costs closer to $3 million. No matter what happened, Jocelyn says, it was obvious “we needed to raise a lot more money.”

One afternoon this summer, I visited Jocelyn and Talia at their modest ranch home in Ipswich. Like any tween, Talia was more interested in hanging out in her room enjoying her iPad than sitting at a kitchen table and talking. She introduced me to her dog, Ivy, told me she’s excited to start the sixth grade—her first year in middle school—and explained that the upside to having once spent six months in a body cast is that everyone signed it. As she snacked on chips and guacamole, she spotted a spider crawling up the wall and urgently alerted her mother. Jocelyn captured the arachnid using a plastic cup and a nearby folder, and Talia briefly inspected it before politely directing her mom to release it outside, unharmed. It could have been a scene from any kitchen with any mother and daughter.

After a few minutes passed, though, it became clear that Talia was fatigued. Small tasks such as lifting food and chewing were exhausting. The further CMT4J progresses, the weaker Talia’s muscles will become.

Before Talia retreated to her room, she spent several minutes hooked up to a cough-assist machine, a small medical device that sat next to the kitchen table. Jocelyn fit the clear ventilator mask snug against Talia’s cheeks and pulled the straps over her thin blond hair. The machine groaned to life and forced a slow and steady stream of air into Talia’s lungs, expanding them like two delicate balloons. Then it clicked loudly and vacuumed the air out of her chest. Talia’s eyes grew wide as she labored through each breath. “When you think about muscles, you don’t think about muscles that are involved in breathing,” Jocelyn explained to me over the mechanical whooshing. “But people with neuromuscular diseases lose those muscles that help them take a deep breath, exhale, or cough. So Talia can’t cough anymore. She can’t take a deep breath.”

A little more than a year has passed since the conference in Maryland, and the Duffs’ progress is undeniable. To date, Cure CMT4J has raised approximately $300,000. With the exception of two small grants, nearly every penny has come from neighbors and friends of friends buying shoelaces and putting on bake sales. The research team the Duffs assembled is in full swing, too, and making headway. After some initial challenges, Gray found a way to fit the FIG4 gene in the viral vector. He packed several vials of the compound in dry ice and FedExed them from North Carolina to Bar Harbor, where Lutz has been busy testing it in mice. Just a few weeks ago, the first preclinical results came back—and they indicate that the gene therapy is working in the animals. “I’m surprised it worked out as well as it did,” Lutz tells me. “We feel really good about this data.”

It’s positive news, but no one’s breathing a sigh of relief. Plenty of experimental medical treatments have looked promising in early studies of mice, only to peter out as testing becomes more rigorous. Jocelyn does her best not to get ahead of herself. She knows the only way to climb a mountain is one step at a time. The Duffs still need to raise at least $700,000 more, and quickly. The foundation is targeting additional grants and just hosted a fundraising gala, but the effort still largely depends on small grassroots donations. While the Duffs have tried social media campaigns, Facebook and Instagram are saturated with cause-driven marketing, and it’s been hard to cut through the noise.

The immediate path forward is paved with toxicology tests that cost nearly $200,000; FDA hearings in Washington, DC; and the potential of a yearlong wait before they can actually manufacture the therapy. While Gray in North Carolina was able to make an initial batch of the viral vector in his lab for preclinical testing, he doesn’t have the equipment or capacity to produce it in the quantity or concentration needed for humans. In fact, he explains, there are probably only about a dozen sites in the world that do, and the recent renaissance of gene therapy has led to bottlenecks at all of them. “Most are booking out a year from now,” he tells me. “The clock is literally ticking. Every day really does matter.”

Nobody can say for sure whether Talia will be here in a year. Since so few cases of CMT4J have been documented and closely monitored, it is impossible for doctors to accurately predict how quickly her disorder will continue to progress. The life expectancy for patients is highly variable: In one case, a 56-year-old man wasn’t diagnosed until after he retired as a firefighter and noticed that the muscles in his hands and feet were acting strangely. In other cases, children began exhibiting symptoms as early as age three.

Jocelyn knows that Talia might not live long enough to reap the fruits of her labor. “My biggest fear is that we’ll have this proof of concept,” she says, “and we’ll not have the money needed to move forward.” Regardless, she is committed to seeing the mission of Cure CMT4J through to the end, knowing that in some small way, Talia’s journey will make it easier for other families to find their paths through the unforgiving world of rare diseases: “I’m hopeful that perhaps in the future people won’t have to do what we’re doing.” Her daydreams of her daughters skipping hand in hand down the street have been replaced by daydreams of a medical center where patients with rare genetic disease are diagnosed and matched to an appropriate treatment right on the spot. “It won’t cost millions of dollars,” she says. “Just go and get your treatment and be on your way.”

Talia has daydreams of her own. There are times when she gets frustrated by her body’s limitations, and she’ll say, “Mom, I can’t walk” or “Mom, I can’t run.” And Jocelyn will tell her that’s why everyone is working so hard to make a medicine for her. And then Talia will let her imagination run wild and say, “Mom, I can’t fly.” And Jocelyn will tell her, “It’s okay, sweetheart. I can’t fly, either.”