The ballroom at the Hilton Garden Inn in Chicago was packed. Families from across the country wore T-shirts with a logo that promised “Strength for Today” and “Hope for Tomorrow.”
Maggie Hoyle-Germann and Anthony DeLuna stood in the doorway, watching the crowd. Dozens of boys were slumped in wheelchairs, lying on stretchers, hooked up to machines — just like their son. Some were teenagers, with thin limbs and long faces, the telltale signs of rare and fatal muscular disorders.
“This is amazing!” Maggie said, squeezing Anthony’s arm. “And so scary.”
Lincoln was 19 months old that summer of 2015. He had been born with X-linked myotubular myopathy, so he couldn’t swallow, sit up or breathe on his own. He was much too fragile to travel.
His parents had left him that weekend, for the first time. Maggie’s sister, Katie, had promised to “take care of Bubba,” so that Maggie and Anthony could attend the second bi-annual conference for families like theirs.
Maggie had invited her aunt and uncle who had raised her; they drove in from Iowa. Anthony’s mother had flown with them from Florida. They wanted to meet boys with Lincoln’s disorder and other parents going through the same ordeal.
They also hoped to hear from the scientists researching cures.
Maggie wanted to make the doctors fall in love with Lincoln, so they would fight to get him into a clinical trial.
Anthony hoped to learn everything about gene therapy, how a treatment would work and what would happen if it failed.
In a mustard-colored meeting room, beneath bright lights, the families sat in long rows, eagerly watching PowerPoint presentations. An hourlong explanation of genetics. A history of finding viable ways of delivering altered genes.
One included a slide of wishes, things parents wanted for their sons:
Hold head up
Maggie looked at all the other families waiting for a miracle. Anthony took notes, untangling the science.
He is a member of MENSA, a society for people with high IQs, and Maggie valued his intellect, his ability to solve the most technical conundrums. He was relieved the doctors didn’t talk down to the parents and appreciated how they explained the pitfalls, as well as the possibilities.
On the second day, they listened to Alan Beggs, a researcher from Boston Children’s Hospital. They heard a French scientist talk about new ways to inject DNA into mice. They saw a researcher who had tracked Lincoln’s breathing at the University of Florida.
He had never thought about becoming a doctor until his wife almost died in childbirth. As he stood there, helplessly watching her hemorrhage, he prayed for God’s guidance. And he decided he could help save bodies as well as souls.
After earning a PhD in physiology at the University of Missouri, Childers moved to North Carolina to do research at Wake Forest University. There, he started extracting stem cells from dog placentas and trying to transplant them to grow replacement genes.
He began working with Anthony Atala, who had recently come from Harvard and had told him about X-linked myotubular myopathy. One broken gene could prevent a boy’s body from making a protein called myotubularin. Without that protein, which connects the brain to the muscles, he can’t move.
With muscular dystrophy, muscles deteriorate. But with XLMTM, boys’ muscles are undamaged, locked in a fetal state.
Now that scientists had discovered, and isolated, the broken gene, someone could clone a copy of the correct gene and inject it into the patient.
But finding a way to deliver the corrected gene into the muscle, or bloodstream, was tricky. Viruses make the best conduits, because they replicate quickly and can transport the new DNA into the nucleus of a cell. But they have to be modified, so they don’t cause adverse effects. Or trigger antibodies.
It was the viral courier — not the new gene — that killed an Arizona teenager in 1999, halting clinical trials in the United States for almost 20 years.
“We kept writing grants. Our grants kept getting turned down, with messages: Gene therapy is never going to work in this dog model,” Childers said. “I thought it was a complete waste of time. I was so frustrated, I was months away from just giving it all up.”
Then Alison Frase found the chocolate Lab in Canada.
Childers took Nibs home, where the dog slept with his daughter on a big bed in the basement.
In a lab at Wake Forest University, researchers began breeding Nibs’ puppies.
Within months, Childers got a call from a nonprofit lab in France called Genethon. Researchers there had been testing gene treatments on mice and had heard Childers had dogs. “I don’t even know how word got out,” Childers said. “We hadn’t even published anything yet.”
If he wanted to collaborate, the French scientists said, they would give him the viral transport they had been working to perfect.
Childers moved his dogs to the University of Washington in 2012, and brought his colleague from Wake Forest, Dr. David Mack. Together, they began giving Nibs’ descendants gene therapy.
“Our first test was a small dose into a puppy’s leg muscle,” Childers told parents at the conference. He showed them video of one of Nibs’ granddogs, a limp black Lab named Rocky. “Within three weeks, the strength in his back leg had doubled. We thought something had gone terribly wrong with the equipment. So we measured again, and the hair on my arms stood up.”
After six weeks, Rocky’s one leg had become as big and strong as a normal dog’s. He was lopsided and alive.
“This protein turns over so quickly,” Childers said.
The next time, instead of injecting the corrected gene into muscle, researchers tied tourniquets onto the hind legs of two other affected puppies and shot into their bloodstreams. Those dogs were named after scientists Pavlov and Turing.
Within a month, the black Labs were leaping over each other, chasing balls.
Those dogs are now 3 years old, Childers told his wide-eyed audience. That one-time treatment seems to have cured them. “You can’t tell them apart from normal dogs.”
It’s impossible to watch the dogs, Mack said, and not imagine boys someday standing up and walking. “That’s my dream,” he said.
A timeline of gene therapy
1859: English naturalist Charles Darwin publishes The Origin of Species, which includes the idea of passing on heritable traits.
1866: Austrian monk Gregor Mendel publishes paper on the principles of inheritance after experimenting on pea plants.
1953: American James Watson and Englishman Francis Crick describe the molecular structure of DNA — a double helix — for which they win the Nobel Prize nine years later. They tie it to the transmission of genetic data.
1970: First published use of the term gene therapy, defined as transplanting normal genes in place of missing or defective ones to correct genetic disorders.
1972: Science magazine explores the possibility of gene transfer, inserting copies of a gene into living cells.
1974: The Recombinant DNA Advisory Committee (RAC) is established at National Institutes of Health (NIH) to develop guidelines for gene research.
1983: First disease gene — for Huntington's disease — is mapped. The Orphan Drug Act creates financial incentives for drug companies to treat rare diseases.
1989: The first human gene transfer experiment takes place at NIH, on a cancer patient.
1990: First successful gene therapy clinical trials, at NIH, improve the immune function of children with Severe Combined Immune Deficiency. NIH launches the Human Genome Project, a $3 billion, 15-year endeavor to map and sequence human genes.
1993: The RAC approves the first commercial trial of gene therapy, permitting Targeted Genetics Corp. to implant genetically modified cells into AIDS patients to boost their immune systems. Scientists identify genes linked to more than a half-dozen major illnesses, including colon cancer.
1995: Nature magazine reports successful gene therapy on three infants. President Bill Clinton creates the National Bioethics Advisory Commission to protect “the rights and welfare of human research subjects.”
1999: Gene therapy suffers a huge setback with the death of 18-year-old Jesse Gelsinger of Tucson, Ariz., during a clinical trial to correct an enzyme defect.
2003: The human genome is completely sequenced.
2015: Nature magazine announces: Gene therapy returns to center stage.
2016: At a conference of the American Society of Gene and Cell Therapy, Audentes announces successful gene therapy on 3-year-old dogs suffering from myotubular myopathy.
2017: FDA approves first gene therapy for leukemia treatment. New York Times announces in October: “In a first, gene therapy halts a fatal brain disease.”
Source: CQ Researcher, Audentes Therapeutics
Childers talked about money — and how a private venture capital firm was helping fund more research. “There’s still a lot to learn,” Childers said, “a lot of hurdles to leap.”
“But we can now dream of things we couldn’t even consider a few years ago.”
Afterward, Maggie rushed through the throng of applauding parents and leaned over the podium to hug the scientist.
“I’m Lincoln’s mom,” she said. “Thank you! Thank you so much!”
She told Childers about finding his YouTube video, watching it so many times she lost count. She pulled out her phone and opened her Facebook page.
She said, “This is Lincoln.”
She clicked on a home video, handed Childers the phone. He saw the boy’s flat face, his slack jaw. Lincoln was in his crib, staring at the ceiling — until Maggie leaned in.
Then Lincoln folded his fingers into “I love you.”
The scientist wiped his eyes.
The last presentation of the day was from Matt Patterson, who pulled a conference T-shirt over his blue button-down and stepped to the edge of the stage.
Three years ago, he told the crowd, he had met Childers and a researcher from UF. They had told him about the promising results from gene therapy that they were seeing in dogs.
“So I formed a bio-technology company: Audentes,” Patterson told the parents. “Our mission is to help develop treatments for rare diseases.”
With money from millionaire investors, he had brought in $73 million so far, he said. He had hoped to have a treatment ready to bring to a clinical trial by now.
But getting permission to try a new drug is a long and complicated process. The product must be tested in laboratories and on animals and proven effective and safe. Then the sponsor has to present those findings to the Food and Drug Administration, along with a plan to start testing on people. If the FDA approves a trial, all that information goes on to the hospitals where the dosing will occur, and an Internal Review Board at each institution has to look over everything. If the IRB approves, the study can start.
Once patients get the treatment, doctors monitor them for at least six months, then turn that data over to the FDA. It can take years for the FDA to approve a new drug — and cost more than $1 billion. About 80 percent of all new drugs never make it to market.
At the time Patterson was speaking at that conference, the FDA had never allowed a gene therapy treatment to be sold.
Even producing the product, Patterson said, was posing problems.
“We’re working hard on manufacturing. It’s incredibly complex. But we’re solving this,” he said. “It’s just taken longer than we thought. It sucks. It’s an incredible disappointment.”
He forced a smile but couldn’t make eye contact with his audience. “We have confidence,” he said, “that we can start in 2016.”
Maggie glanced at Anthony. By then, Lincoln would be 3. Double the time he had survived so far.
Senior news researcher Caryn Baird contributed to this story.