From the age of three, Tara Radcliffe Ghiglieri danced almost every day, leaping, pirouetting, tapping, and high kicking her way into a Broadway career that included a multi-year stint as a Radio City Rockette.
She trained hard, at times rehearsing eight hours a day, six days a week.
“And performance days could be up to six shows in a single day,” Radcliffe Ghiglieri said. “It was like running a marathon every day.”
Gene therapy
Like any elite athlete, her body took a beating. Over time, it wasn’t just muscle soreness. During a synchronized high‑kicking performance with the Rockettes, she hyperextended her knee. After that, both knees hurt, but her left knee often ballooned after long performances.
A former professional dancer and mother of two, Radcliffe Ghiglieri joined an early clinical trial at UC San Diego to treat her knee osteoarthritis.
Her story is familiar to serious athletes and weekend warriors alike — old injuries and overuse building into osteoarthritis that worsens over time. Now, a new gene‑therapy approach in clinical trials, backed early on by the California Institute for Regenerative Medicine, may offer hope. The treatment being tested by the company Genascence aims to block inflammation, pain, and cartilage damage, and Radcliffe Ghiglieri is among the first patients to receive it.
In her early 30s, a doctor told her she’d likely need a double knee replacement within ten years. The pain was constant. Retiring from dancing and moving to the West Coast didn’t help.
“If I took time off and then went back to a dance class, my knee would swell to the size of a cantaloupe,” she said. “It would last for days.”
She adjusted her life around the pain. Even simple things — sitting through a movie or climbing stairs — could be intensely uncomfortable. She still hiked with her husband and two young kids or joined an exercise class, knowing she would pay for it afterward.
For someone who had built her life around movement, the problem felt existential.
“I think about my knees a lot,” she said. “And you shouldn’t have to.”
High cost of knee osteoarthritis
Knee osteoarthritis is rarely counted among major public health issues, yet it carries enormous personal, health, and economic costs.
An estimated 32 million Americans and 3 million Californians have the progressive joint disease. It is a leading cause of disability worldwide, with knee joints most often affected. Along with pain, people may experience stiffness, swelling, and even “a crunching feeling” of bone rubbing on bone, according to the NIH.
These symptoms can limit mobility and trigger a cascade of additional health problems. As the condition worsens, cartilage breaks down, and joints can become unstable.
The direct healthcare costs of knee osteoarthritis—doctor visits, imaging, and surgery—account for more than 4 percent of total U.S. healthcare spending. Knee replacement surgeries alone can range from about $39,000 to $195,000, according to research published in the Journal of the American Academy of Orthopedic Surgeons.
Genascence estimates that the combined direct and indirect annual costs exceed $8 billion. The clinical‑stage biotech aims to use gene therapy to treat musculoskeletal disease.
Radcliffe Ghiglieri was among more than 60 patients who participated in early clinical trials testing gene therapy for knee osteoarthritis. The treatment, GNSC‑001, is a single injection into the knee that reprograms local cells to produce an anti‑inflammatory protein, with the goal of long‑lasting relief.
The company’s Phase 1b trial, called DONATELLO and funded in part by a $12 million CIRM award, showed promising results. Genascence now plans a much larger Phase 2b/3 trial, which could begin in 2027.
Entering the clinical trial
Radcliffe Ghiglieri didn’t know much about the science, but she knew she didn’t want to live in pain—or face a future of worsening cartilage loss, joint degeneration, and an eventual knee replacement.
She began looking into potential treatments, many of them unproven.
“It felt like a lot of money for something that might not work,” she said.
When she moved with her family to San Diego a little over three years ago, something unexpected happened: a clinical‑trial notice targeting knee osteoarthritis popped up on her social media feed. The study run through UC San Diego’s Alpha Clinics — part of CIRM’s statewide clinical care network — immediately caught her attention.
It wasn’t some wellness clinic,” she said. “It was a real study, and it was at the University of California San Diego.”
She met all the criteria: over 40, with moderate osteoarthritis confirmed by X-rays.
The treatment involved a single injection into her knee, along with a short course of prednisone around the procedure. At first, she worried she’d made a mistake.
“I’ll be honest, the pain was intense,” she said. “I couldn’t straighten my leg or walk normally.”
Fortunately, the discomfort passed quickly.
“Almost overnight, it just went away.”
Within three months, something unexpected happened—she realized she’d stopped thinking about her knee.
“That’s how I knew something was different,” she said.
Measuring change
As part of the clinical trial, Radcliffe Ghiglieri returned for regular follow-up visits at 1 month, 3 months, 6 months, 1 year, and 2 years. During each visit. researchers monitored her symptoms and analyzed synovial fluid from her knee joint. The fluid plays a key role in joint lubrication.
Before treatment, the fluid was thin and watery. Afterward, it became thicker, more viscous, and golden. At each check, those changes indicated the treatment was working; more importantly, Radcliffe Ghiglieri wasn’t feeling pain and had improved joint function.
Meanwhile, Dr. Susan Bukata, Chair of UC San Diego Health’s Department of Orthopedic Surgery, said she was surprised by the improvements in trial participants under her care. Participants in the trial had less pain and more function. In addition, the biomarkers present indicated that the treatment triggers the production of a protein in the treated joint that blocks inflammation, pain, and cartilage damage.
“What was most remarkable was the dramatic improvement we saw within the first six months,” said Dr. Bukata in a video presentation to the CIRM board in June.
Radcliffe Ghiglieri said she didn’t need the checkups to confirm that, at least for her, the treatment was working.
After six months, Radcliffe Ghiglieri led a two-hour dance class for a school fundraiser. She’d been unable to do that since retiring from dancing years ago.
“I was prepared for my knee to blow up afterward,” she said. “And it didn’t. No swelling. No inflammation. Nothing.”
A broader impact
Radcliffe Ghiglieri’s experience reflects that of a participant in an early-stage clinical trial. However, researchers caution that the FDA has not yet approved the therapy and that it may not work for everyone.
Looking ahead, Genascene plans to begin a much larger Phase 2b/3 clinical trial in 2027. Following that, the FDA will review the results from that much larger trial to consider whether to authorize the treatment.
Even so, for Radcliffe Ghiglieri, the experimental treatment highlights the potential of gene therapy to address not just rare conditions but more common, chronic conditions such as osteoarthritis.
“This isn’t a rare disease,” she said. “This affects so many people.”
Beyond that, Radcliffe Ghiglieri felt lucky to have access to such an innovative clinical trial so close to home. In her view, the idea that her participation in the clinical trial could lead to an FDA-approved treatment is a bonus.
“I believe in this kind of science,” she said. “If something like this can help people avoid major surgery and long recovery times,” she said, “that’s huge. It’s worth it.”
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