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

Xconomy National — 

[Updated, 4/22/19, see below] If a once-modest regional hospital and its new biotech allies have their way, the capital of Ohio could one day rival America’s other biomedical hubs.

“Our goal is to make Columbus the center of the universe for gene therapy,” says Doug Ingram, CEO of Sarepta Therapeutics.

Sarepta (NASDAQ: SRPT) is based in Cambridge, MA, as you might expect from a high-flying biotech company. But it plans to open an 85,000 square-foot gene therapy center with 100 employees in Columbus, tapping into a wide-open pipeline from Nationwide Children’s Hospital. Earlier this year, Sarepta bought a startup that spun out of Nationwide to grab five experimental gene therapies developed at the hospital, adding to three others it had already acquired from Nationwide since 2017.

Sarepta isn’t Nationwide’s only new biotech friend. The hospital has signed 28 licensing deals since the start of 2018, a stunning amount for an entity that, two decades ago, had barely any in-house research of its own. Thanks to ambitious officials, a risk-taking administration, and a tight connection between its labs and its hospital practice, Nationwide has become a gene therapy leader. “They’ve been unbelievably productive,” Ingram says.

Nationwide really got started, in fact, when much of the field was shutting down after an infamous death during a gene therapy clinical trial. “It looked like it had no future, people were really frightened,” says Jerry Mendell, the longtime director of Nationwide’s gene therapy center and a pioneer in the field of neuromuscular disease research. “What we started here has had an incredible impact.”

The hospital’s appetite for risk and Mendell’s persistence could lead to one hell of a coming-out party. In clinical tests, the spinal muscular atrophy treatment Zolgensma, developed by Mendell’s team and already the centerpiece of an $8.7 billion buyout, has given infants with a probable death sentence a chance to live, grow, and thrive.

Zolgensma could soon become just the second gene therapy approved in the U.S. Its new corporate owner, Novartis (NYSE: NVS), has hinted that it could also become the most expensive drug of all time. If a single dose of Zolgensma turns into a cure, as is the hope for this and other gene therapies, it could upend the way doctors treat SMA. In short, it will be a crucial test case for the medical, social, and financial viability of gene therapy.

After flying under the radar all these years, Nationwide is now squarely on the national map.


Phil Johnson needed a star.

Johnson came to Nationwide in 1991 after a four-year stint running the National Institutes of Health’s infectious disease laboratory. Nationwide was a small-town hospital then. It paled in comparison to children’s hospitals in Seattle, Boston, Philadelphia, and nearby Cincinnati.

But Nationwide’s board had broader ambitions, a reflection of Columbus’s own historical ascent as a major U.S. city. Columbus has long been an industrial hub and a major academic presence because of The Ohio State University. (Yes, they insist on the “The.”) Between 1950 and 2000 as suburbs sprouted up around Columbus, it annexed more than 150 miles of nearby land and grew considerably, building a diverse economy that went beyond its industrial roots. Since the 1960s, its population has nearly doubled to almost 890,000, putting it 15th in the country, just behind San Francisco.

Johnson was hired and quickly began pushing hospital administrators to make Nationwide similarly known, well, nationwide for its research. “They saw that the way to take the hospital to the next level was to invest in research and academic medicine,” says Johnson, now the chief scientific officer of a stealthy Philadelphia gene therapy startup called Limelight Bio.

These were the early days of gene therapy, which uses viruses to shuttle genetic instructions into the body to fix a genetic disease. The first human tests had just begun. Johnson wanted to hire high-profile researchers and entice them with a focus, he told the board, on “genetic medicine,” a broad term that included what would come to be known as gene therapy. If they could invest in the work, the scientists would come, and Nationwide would no longer have to send Columbus kids elsewhere to get treated. “They could go back to the community and say, ‘look what we’re doing for you,’” Johnson says.

At the NIH, Johnson had been involved in early research using adeno-associated viruses (AAVs) as a way to deliver potential therapies into cells. He brought that interest to Nationwide.

But it was tough to make the amount of engineered virus needed for animal testing. The amount for testing in humans, if they ever got that far, would be even greater.

Johnson and his first hire Reed Clark, who had earned his PhD in molecular genetics from Ohio State, began working on ways to produce AAVs more efficiently and in greater batches. They convinced the board to back their efforts.

“The research budget started to climb year after year,” says Clark, who is now a senior VP of gene therapy at Ultragenyx (NASDAQ: RARE). “And that was really due to Phil’s persistence.”

Then the gene therapy field ran into tragedy.

In a now-infamous study, an 18-year-old Arizona teenager named Jesse Gelsinger died in a gene therapy trial at the University of Pennsylvania in 1999. The news sent shockwaves through the sector. The FDA suspended trials. Investment chilled.  Startups crashed. And the work of a researcher named Jerry Mendell, the chair of neurology at Ohio State, ground to a halt.

“Basically all of gene therapy got shut down because of the death of this young man,” Mendell (pictured below) says.

A neurologist by training, Mendell for decades has treated kids with deadly neuromuscular diseases like Duchenne muscular dystrophy and spinal muscular atrophy. Until recently, they had no FDA-approved treatments and still don’t have cures. “He diagnoses them and sees them pass [away],” Clark says of Mendell. “It’s hard to articulate what that’s like. I’ve tried to wrap my brain around it.”

Mendell doesn’t just treat sick kids. He does lab work, too, and has … Next Page »

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