Knee joint pain rarely gets counted among major public‑health burdens. Yet it affects more than 3 million Californians and 34 million people across the U.S., with both massive economic and health consequences.
Costly Impact
In California alone, the cost of knee replacement surgeries exceeds $8 billion annually, according to Thomas Chalberg, PhD, founder and CEO of Genascence.
The company, a clinical-stage biotech that aims to use gene therapy to treat musculoskeletal disease, is currently focused on knee osteoarthritis because it is so prevalent, debilitating, and lacks a cure.
“Patients are left in a zone of pain and compromised mobility but with no effective treatment to slow down or stop the disease,” said Chalberg.
As those living with knee osteoarthritis cope with pain and compromised mobility, other co-morbidities can spiral, he said.
“It is the number one cause of disability,” Chalberg said. “The top cause of chronic pain. A top cause of opioid use and abuse.”
CIRM’s funding
He offered up those grim stats at a California Institute for Regenerative Medicine (CIRM) board meeting in June, while also highlighting progress on a possible gene therapy for the condition now in clinical trials.
The company’s Phase 1b clinical trial, dubbed Donatello and funded in part by a $12 million CIRM award, showed promising results, prompting the company to prepare to move into a Phase 2b/3 trial that would include many more patients. If the treatment works, Chalberg suggested it could save as much as $2.5 in health care costs in California.
Board member Ysabel Duron asked about those savings.
“You said this would save a lot of money in health care costs, but how much will (the treatment) cost patients?”
Chalberg answered that he did not yet know. However, because the company has improved the manufacturing process for creating the gene therapy, he believes it will be affordable for most patients.
“Our goal is to make this broadly accessible and available for the cost of less than a joint replacement,” he said.
What is Knee Osteoarthritis
Osteoarthritis is a progressive joint disease and a leading cause of disability worldwide, with knee joints the most affected. Causes include repetitive use or injury, as well as genetics or weight.
Beyond pain experienced by those with osteoarthritis, the symptoms include stiffness, swelling, and “a crunching feeling or sound of bone rubbing on bone,” according to the NIH. Together, these symptoms often limit mobility, leading to a cascade of health problems.
Typically, treatments focus on symptom management, such as pain relievers and steroid injections, with full knee replacement as an option if pain management isn’t successful. There is no cure. Are they the most affected? Or just the most costly due to knee replacements?
According to the NIH site and what he said last night, knees are the most affected.
The gene therapy approach
Genascence wants to change that, said Chalberg.
Using a gene therapy known as GNSC-001, Genascence injects a harmless virus, an adeno-associated virus, into the knee joint to deliver instructions to cells to produce the protein interleukin-1 receptor antagonist (IL-1Ra). This protein blocks the signal that triggers inflammation, pain, and cartilage damage, all associated with osteoarthritis.
The treatment is given as a single injection directly into the knee joint. The idea is that once the cells in the knee start producing this protein on their own, it could provide longer-lasting relief than current knee injections.
Before undertaking the clinical trial in humans, the group tested the approach in animals, including horses, with promising results.
But what about people?
The human trial, Donatello Phase 1, included 67 people with results showing the treatment to be safe and well tolerated, Chalberg said.
That early-phase trial also showed other encouraging signs. Participants in the trial had less pain and more function. The biomarkers present indicated that the treatment triggers the production of a protein that blocks inflammation, pain, and cartilage damage.
“What was most remarkable was the dramatic improvement we saw within the first six months,” said Dr. Susan Bukata, a board-certified orthopedic surgeon at UC San Diego. Dr. Bukata worked on the clinical trial and spoke in a video Chalberg showed during his presentation.
Her comments came in a video presented to the board. Although anecdotal, her comments highlighted that, for at least two of the patients in the clinical trial, the treatment was already life changing.
UC San Diego is also one of nine CIRM-funded Alpha Clinics across California. Alpha Clinics carry out cell and gene therapy clinical trials.
What’s next
After finishing that successful trial, company officials met with the FDA. In that meeting earlier this year they outlined the design of a Phase 2b/3 trial, considered a pivitol trial. The company hopes to begin later this year or in 2027. The FDA also designated the company’s GNSC-001 treatment what is called a Regenerative Medicine Advance Therapy (RMAT) designation. The designation gives it a potential fast-track for development and review.
More on Closer to Cures
Closer to Cures is a speaker series that features presentations from CIRM-funded awardees at each meeting of the California Institute for Regenerative Medicine’s governing board. The governing board is known as the Independent Citizens Oversight Committee (ICOC). The meetings and this speaker series are open to the public and are livestreamed via YouTube.
Watch the full presentation:
https://youtu.be/qI26x3XKm1
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