On Thanksgiving Day 1998, a geneticist called Donavon Decker and told him the lab had identified the gene that was causing his and his sisters’ muscles to slowly deteriorate. By the way, the geneticist added, this might be a good candidate for gene therapy.
Decker called back every month until April, when the researcher finally put him in touch with neurologist Jerry Mendell. Mendell said Decker could be of service — but that he couldn’t help Decker.
Gene therapy was still new and risky. No muscular dystrophy patient had ever received one. To assure safety, Mendell would only inject a tiny foot muscle. Decker wouldn’t benefit. He could be harmed and might be rendered ineligible for future gene therapies. But if it worked, it could advance the field, including for his four sisters with the disease.
“He put his foot out,” Mendell recalled, “and said ‘go for it.’”
Decker died Monday at age 62. There are today still no treatments for his condition, known as limb-girdle muscular dystrophy (LGMD). But Decker’s study paved the way for gene therapy’s resurgence over the past decade, including approval of the first gene therapy for spinal muscular atrophy and Duchenne, the most well-known and fatal form of muscular dystrophy.
That trial “really set the stage for everything that came afterwards,” said Sharon Hesterlee, a longtime friend of Decker as well as interim head of the Muscular Dystrophy Association (MDA), which sponsored the 1999 study.
He died of complications from an elevator accident, exacerbated by the toll the disease had taken on his lungs.
Those in the muscular dystrophy community remembered a fearless and indefatigable advocate who set an example and served as a resource for other parents and patients. “I could cry just talking about him,” said Kelly Brazzo, whose daughter has LGMD. “He moved the gene therapy field forward without ever seeing a benefit himself, just a heroic and selfless act.”
The excitement over Decker’s study faded fast. Three days after his injection, he and Mendell appeared on the Jerry Lewis MDA Telethon, where they both spoke about the promise of an imminent cure. Less than two weeks later, 18-year-old Jesse Gelsinger died in a misstep-ridden trial at the University of Pennsylvania. The field, including the LGMD study, shut down overnight.
Decker, though, remained a force in the community. In 2001, he testified before Congress to push for the MD Care Act, a bill that dramatically expanded federal investment into muscular dystrophy, and served on the research coordinating committee the law created.
Mendell, who in 2004 became director of the gene therapy center at Nationwide Children’s Hospital, kept working too, relying in part on data from Decker’s foot. It had been one of the first studies to try to ferry genes into the body with a new, potentially safer group of viruses, called AAVs, than the one Gelsinger received.
Although the results weren’t a home run — the dose was infinitesimal — it showed they could safely deliver genes into muscle, Mendell said. Although he never published the data, he said he used it when submitting applications to the Food and Drug Administration.
In 2013, as the gene therapy field began its modern resurgence, Mendell was ready to start a new trial for Decker’s subtype, called LGMD 2D, this time infusing a full leg, through the blood stream. There are dozens of LGMD subtypes, each tied to a different gene. LGMD 2D, while ultra-rare, had been chosen because it was more common than others, and the gene could fit snugly into viruses.
Decker volunteered again. But a blood test showed he still had antibodies from the 1999 trial. They would block the gene therapy, which used the same category of virus. “So he asked me if I knew anyone else that would do [it],” Decker recalled at a speech at the MDA’s conference earlier this year, when he was given an MDA Legacy Award for Community Impact in Research.
His sister June Burney stepped forward, becoming the first muscular dystrophy patient to receive gene therapy through the new system. She saw some benefit, Decker recalled, but then regressed.
Mendell moved to dose patients systemically, the approach that would eventually lead to Elevidys, the gene therapy for Duchenne. But that’s where LGMD efforts began sputtering.
After promising early results in LGMD 2E, Sarepta Therapeutics bought out a startup spun out of Nationwide to develop one-time treatments for five different subtypes. But it did not move most of those programs forward, including the 2D treatment, for years, spending most of its resources on Duchenne.
The delays frustrated Decker. Fellow advocates described him as a kind, soft-spoken man, with ample time, support, and wisdom ready, including for those facing a new diagnosis. And he had a humorous streak: He often recounted how, at the end of his hospital stay for Mendell’s trial, he yelped in pain when Mendell poked the site of the injection — the doctor jumped back, terrified the gene therapy had gone horribly awry, only to look up to see Decker laughing. But he could be a fierce advocate when he felt LGMD patients were being left behind.
LGMD is often described as a less common and less severe form of muscular dystrophy. But he saw the toll the disease could take. In the years since the 1999 trial, he became fully reliant on his wheelchair and had to leave his job as an air traffic control specialist. He lost three sisters to the disease, which slowly sapped strength from their lungs. “They don’t understand the urgency,” he said in a documentary, “In Search of Strength,” about his life that came out this year.
“Sometimes I feel overwhelmed when I see nothing happening, and I can see how some companies are not working on the research like they say they do,” he said. “That makes me angry at times and sometimes it gets the best of me, but it also makes me a strong advocate.”
He kept testifying, explaining to the Food and Drug Administration the abilities the disease had taken from him and advocating for the agency for flexibility in ultra-rare diseases.
And he encouraged other advocates to not leave their full faith in companies. Joe Dion remembered meeting him in 2023, when Sarepta was working on a gene therapy for LGMD 2C, a condition both his children were facing.
Decker encouraged Dion to remain skeptical, advice that led him to fund an alternative gene therapy effort. Both of his children have been dosed this year, while Sarepta, facing financial challenges and the death of a patient in another LGMD trial, pulled away from the disease altogether.
“If that wasn’t for him” his kids would never have been treated, said Dion. He credits the treatment with giving his 12-year-old son, Peter, who had been declining, the strength to get his student lobster license this summer and pull up traps at 7 a.m.
Before Decker died, he was trying to figure out how he could buy Peter’s lobster and have it transported frozen across the country, to his home in Kansas.
Decker was also working on his own approach. At one point, he helped another company with interest in LGMD raise nearly $5 million, Hesterlee, the MDA chief, recalled. That company pivoted away, but Decker started his own company, focused on a new non-viral gene therapy approach that might help older patients like himself and his sister June. He recruited top scientific leaders like Hesterlee to advise.
“And the fact that the company had no money didn’t faze him at all,” said Hesterlee. “You don’t underestimate Donavon ever, that was my advice to anyone. Sure. You know, he sounds like a Midwestern guy. He’s got kind of a low-key, slow way of talking. … Don’t let that make you think that he can’t make things happen, because he really could.”
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