How Far Would You Go to Save Your Little Girl?

At nine years old, Talia had grown into a fairly typical child, with friends, homework, and a bottomless appetite for Disney movies. In school, she kept up with her assignments with the help of teacher assistants and a modified curriculum. Then, in September 2015, days after Talia started fourth grade, Jocelyn was at home when the phone rang. The results from the screening were in. She had something far worse than anyone had anticipated.

Doctors determined that Talia had an obscure genetic mutation associated with a disease called CMT4J, sometimes referred to as a slower form of ALS (and occasionally misdiagnosed as such). Jocelyn had never heard of it. As it happened, neither had most of the medical community. CMT4J, a subtype of the degenerative Charcot-Marie-Tooth disease (CMT), is so rare that Talia is one of only 22 people in the world known to have it. Though Jocelyn initially tried to resist the urge to Google it—“I was really afraid to learn more,” she says—she quickly succumbed. Her stomach churned as she plugged the alphanumeric disease name into her browser. In mere moments, she learned that in addition to being exquisitely rare, CMT4J is considered fatal. “The first thing I read was pretty heartbreaking,” Jocelyn says. “There was no treatment, no cure. Suddenly, I was left to watch my child just get weaker and weaker and fade away.”

In what felt like an instant, the Duffs had been thrust into the heartbreaking realm of rare diseases, where treatments are few and money for research is hard to come by. As it turns out, there are thousands of rare diseases that affect hundreds of millions of people around the world. Yet pharmaceutical companies aren’t exactly racing to develop specialized drugs that only a relative handful of people need. The National Institutes of Health has an Office of Rare Diseases Research to address the need, but resources are limited and there are scores of patients who have been left to their own defenses. In the great cost-benefit scheme of modern medicine, the math doesn’t add up, so families like the Duffs are often told to make their loved ones comfortable and prepare for the worst.

Despite the grim prognosis, the Duffs refused to sit by and watch their younger daughter die. Together, John and Jocelyn spent days and nights in the glow of a laptop researching Talia’s assailant, determined to discover a lifeline. Then, after several weeks of searching, they found one.

In the fall of 2015, the office of neurologist Jun Li at Vanderbilt University received a call from a woman near Boston. Li’s assistant told her that the doctor’s schedule was full and that the earliest available appointment was six months away. Jocelyn was willing to wait. She scheduled the visit and then booked four tickets to Nashville.

For the past 20 years, Li had been researching Charcot-Marie-Tooth disease, a hereditary disorder that attacks the peripheral nervous system and, as it advances, causes the body’s muscles to stop working and waste away. The name of the disorder comes from the trio of 19th-century neurologists—Jean-Martin Charcot, Pierre Marie, and Howard Henry Tooth—who discovered it in 1886. Yet more than a century after Charcot wrote about the curious muscle atrophy that he’d observed in his patients at Paris’s Salpêtrière Hospital, modern researchers, including Li, have only begun to understand the disorder. What doctors do know is that CMT is monogenic, meaning that each type is caused by a mutation on a single gene—which also means that there are dozens of variations. There are CMT1A, CMT1X, and CMT2B, for instance. Their symptoms manifest differently and range in severity. Some forms of the disorder can even be managed with physical therapy, leg braces, or walkers, but there is no cure.

While there is no good type of CMT, Talia’s CMT4J is among the worst. Caused by a mutation on the FIG4 gene, it disrupts the internal traffic signals of human cells and causes harmful microscopic bubbles to spring up across them. As an article in the Public Library of Science’s journal once explained, a cell without a functioning FIG4 protein is like “a city without cabs and trash collectors. It shuts down.”

Over the course of his career, Li has met 11 patients afflicted with CMT4J, and he says it never gets easier. “It’s devastating,” Li tells me. “It’s psychologically very difficult.” When the Duffs arrived at Li’s clinic, it was clear that Jocelyn was anxious. But she had done her homework and she peppered Li with questions. Impressed, Li was polite but direct: “I told them it’s pretty serious,” he says, “and that many patients progressively deteriorate.” After a few minutes, Jocelyn asked what all parents want to know: Was there any treatment? Li paused for a moment. “There is no treatment at this point,” he told the family. “The only thing I can think of that might alter the disease’s progression is gene therapy.”

Gene therapy is basically a biomedical Trojan horse: Scientists package healthy genes inside a harmless virus—or what’s called a “viral vector”—and inject the patient with millions of copies of it. Once inside the body, the virus links up with a cell and delivers the healthy genes. As Li saw it, if there was any upside to the problem before them, it was this: They already knew that FIG4 was the gene responsible. “You have a clear starting point,” he said. “If we can replace the FIG4 proteins, it would theoretically cure the disease.”

Li figured that this basic blueprint could be applied to Talia’s troubled FIG4 gene by injecting her with a viral vector carrying healthy genes. After all, he reasoned, the approach was already being used in experimental studies of a disease called spinal muscular atrophy, and the early results looked promising. He had every reason to believe gene therapy might also help Talia. What other options were there?

Li knew he was offering the Duffs a long shot. Gene therapy isn’t a magic bullet—science’s ability to modify human DNA is a recent development, and treatment is still experimental. In the last few decades, countless headlines have championed gene therapy as the miracle cure for everything from Alzheimer’s disease to blindness, but actual progress hasn’t kept pace with the hype. In recent years, however, gene therapy trials have been on the rise, and the treatment reached a milestone in August when the FDA approved the first gene therapy in the country for children with a rare type of blood cancer.

Still, the hurdles before them were staggering. How would the Duffs even start Talia on such a treatment? It wasn’t as if Li could write a prescription for two doses of gene therapy that Jocelyn could fill at the neighborhood CVS. If they really wanted to do it, the Duffs would have to find specialized labs to bundle the FIG4 gene inside a viral vector; they would need to breed generations of mice with CMT4J in order to test the approach and prove it worked; and even if somehow they managed to show it was effective, they would still need to convince the FDA to let them use an experimental treatment on their child. This wasn’t a matter of persuading an insurance company to pay for an MRI or starting an Indiegogo campaign to cover the cost of chemotherapy. This was about a family of four from the suburbs doing the work of a small-cap biotech company to save the life of their younger daughter.

Careful not to kindle false hope, Li underlined that he’d been speaking about gene therapy in purely theoretical terms. Despite his cautions, though, this was the moment Jocelyn had been waiting for. For months she had been repeatedly told that there was no cure for Talia. Now, a whole new world of possibility opened up before her.

That night, back at the hotel near Vanderbilt, Jocelyn left John and the kids in the room and walked over to the business center. The Duffs were one of only a few families on Earth currently grappling with CMT4J, but they were hardly the only ones to have faced a rare disease—and there were people out there who’d beaten them. Bathed in the glow of the computer screen once again, Jocelyn began researching families who had managed to fight against supposedly incurable ailments.

A common denominator soon emerged: money. They would need a lot of it if they wanted to make a cure. By morning, a path forward had formed in her mind, and on the flight home to Boston, Jocelyn and John began brainstorming a list of friends who could help them get a nonprofit organization up and running.

They knew full well what they were up against. It can take a pharmaceutical company several years of research and hundreds of millions of dollars to advance a treatment to the point where it can be given to patients. And even then, it might not work. But none of that mattered to Jocelyn and John when they touched down at Logan. For the first time in months, they had reason to hope.

Rare diseases—defined as those affecting fewer than 200,000 people—are more common than you might think. To date, more than 7,000 different types have been identified, and doctors discover new ones each year. Some afflict tens of thousands of people while others affect just 10 or 20. Taken as a whole, though, more than 350 million people worldwide are huddled under the rare-disease umbrella. By some estimates, that’s more than the number living with AIDS and cancer combined. With so many people desperately in need of a cure, this might seem like a natural opportunity for a pharmaceutical gold rush. From a business perspective, though, rare diseases are fraught with downside and risk.

For one, says Zak Kohane, a Harvard Medical School professor who leads the Coordinating Center for the Undiagnosed Diseases Network, it’s hard to build a company around customers who are rarities, and few biotech firms are willing or interested in investing in ultra-rare disorders such as CMT4J. Even diagnosing a rare disease can be difficult. As Kohane notes, most doctors aren’t trained to spot such medical outliers, and there aren’t enough patients for scientists to collect the data needed to really understand how the disease presents itself and works. As such, it often falls on the families of patients to become the experts and push for research and a cure. “They’re the ones who feel the pain most acutely,” Kohane says. “If you’re a parent, you want to bring down the house to take care of your kids.”

There are plenty of instances in which parents have gone to extraordinary lengths in hopes of finding a cure for their child’s illness. Perhaps the most famous is the story of Augusto and Michaela Odone, whose quest to save their son was immortalized in the Academy Award–nominated film Lorenzo’s Oil (the oil being the medicine that the family invented and patented). Then there’s Karen Aiach, a successful audit specialist at Arthur Andersen. After doctors diagnosed her daughter with Sanfilippo syndrome A, she started her own biotech company to pursue gene therapy treatments for her. There’s also computer scientist Matt Might, whose social media efforts to diagnose and find a treatment for his son’s rare genetic disease resulted in a precision medicine algorithm that caught the attention of national media outlets—and the Obama administration. Now Might is heading up the newly launched Personalized Medicine Institute at the University of Alabama at Birmingham. These, of course, are the exceptions. For many families, a rare-disease diagnosis is emotionally crushing and can leave them feeling adrift in a system that has nothing to offer, with no one to turn to.