How an Ohio Kids’ Hospital Quietly Became Ground Zero for Gene Therapy

How an Ohio Kids’ Hospital Quietly Became Ground Zero for Gene Therapy

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devoted his life to muscular dystrophy research, including a quest for a gene therapy. In 1999, Mendell became the first to test a gene therapy for a neuromuscular disease—Limb-Girdle muscular dystrophy—in humans. It was “modestly successful,” he says, but in a post-Gelsinger world, the work couldn’t continue at Ohio State. “I tried to revive the program on campus and met considerable resistance,” he says.

Johnson and Mendell had been friends for years; both were Ohio State faculty. Mendell was the star that could put the hospital on the map, but Johnson wouldn’t raid a local university. He just planted seeds from time to time. “Jerry, let me know if you ever want to step down,” he’d say.

Mendell became frustrated with his lack of progress at Ohio State. He was intrigued by Nationwide’s gene therapy work, which had continued at the newly christened Center for Gene Therapy. Despite the Gelsinger tragedy, the administration was convinced to keep going.

Mendell credits Johnson for convincing the administration. Johnson downplays his influence. “Everyone was still on board,” he says. The reason: Nationwide was working with AAV, not the other virus, adenovirus, that killed Gelsinger. “If you understood the science and the circumstance I think it was explainable,” he says.

In 2003, Mendell and Johnson met for lunch. “I asked him a single question: What do you want to do with the rest of your career?” Johnson recalls. “He said, ‘I want to cure muscular dystrophy.’ And I said, OK, let’s do it.”

Mendell gave Johnson a list of the things he’d need to succeed. Johnson barely remembers what was on it. “It was not a negotiation,” he says. “It was just about getting Jerry.”


Soon after Mendell came aboard, Johnson had a surprise. He was leaving Nationwide for the Children’s Hospital of Philadelphia, which had emerging gene therapy work of its own. He walked into Mendell’s office and said, “You’re the new director.”

“I didn’t come down here to be the director,” Mendell responded. “I came down to do research.”

But Mendell took the job and used it to align the center with his personal mission: to treat kids with neuromuscular diseases. He recruited Brian Kaspar, Louise Rodino-Klapac, Zarife Sahenk, and other PhDs with experience or interest in the role AAV could play in gene therapy.

The idea was for scientists to work closely with Nationwide’s clinicians, to move lab discoveries quickly towards human testing. Rodino-Klapac, for instance, began on Duchenne and Limb-Girdle gene therapies right when she arrived in 2005, working alongside Mendell, who sees muscular dystrophy patients at Nationwide. Mendell is currently the lead investigator for the experimental treatments Rodino-Klapac developed. That closeness “enables things to move faster,” she says.

Mendell schooled his crew on the ins and outs of early drug development, including medical oversight boards, regulation, and the packages of data needed to move a medicine into human trials. They ran experiments that failed. They learned, incorporated their findings, tried again, and did better, Rodino-Klapac says. What Clark calls an “early biotech startup” began to form with various capabilities one might find within a life sciences company. “We didn’t even realize it,” Clark says, “It grew organically.”

Mendell and Johnson recruited Kaspar in 2004 from the Salk Institute for Biological Studies in San Diego, where he had been doing work with AAV viruses. Mendell’s focus on close relationships between clinicians and scientists was important. “We clicked early on,” Kaspar says, “and I think we did some magical work together.”

That work started with manufacturing. Kaspar says it became clear early on that Nationwide had to make its own AAV viruses. Outside products cost too much and weren’t reliable. Mendell and Clark had to talk the hospital board into funding an in-house manufacturing facility.

Clark and Mendell pleaded their case for months, telling their story over and over again, detailing the costs and length of studies, the potential revenues from products, and the grant funding the hospital could attract. They finally got $2 million for a small facility that opened in 2009. From there, Nationwide “took off like a rocket,” Mendell says.


One evening in 2008, Kaspar was about to head home when there was a knock at his office door. It was his labmate, Kevin Foust, who would go on to become a neuroscience professor at Ohio State. “You’re never going to believe what I’m about to show you,” Foust said.

To that point, Kaspar had … Next Page »

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