UCLA Health clinicians and scientists are working to change the trajectory of osteoarthritis (OA) treatment from a prevention and treatment-of-symptoms model to regeneration of the entire joint. It’s part of a multi-institutional “moonshot” effort aimed at developing a groundbreaking treatment that is accessible, affordable and available in the shortest possible timeframe.
Currently, there is no cure for OA, a degenerative joint disease affecting 32.5 million people in the U.S. It causes pain, immobility, disability, and many downstream health and financial burdens. Additionally, OA exacts a national financial weight approximated at $136 billion annually.
Such a massive unmet health need requires an equally mighty effort to quell it. Enter the Advanced Research Projects Agency for Health (ARPA-H) Novel Innovations for Tissue Regeneration in Osteoarthritis (NITRO) program. Under this program, UCLA in collaboration with Duke University and Boston Children’s hospital was awarded up to $33 million to complete a project seeking dramatic changes in OA care.
“The funding provided by the NITRO program allows us to promote a novel concept,” explains clinician-scientist Thomas Kremen, MD, orthopedic surgeon and faculty member at the David Geffen School of Medicine at UCLA. “Project criteria require the development of therapy that regenerates bone and cartilage and targets joint tissues through a once-yearly injectable product. The goal is to go from concept to completion of an FDA phase 1 clinical trial within five years. In medicine, that’s the speed of light.”
The right setting
The UCLA team considers all components of the joint holistically, as a single organ. The hope is to identify biologics that heal and regenerate joints to the point of possibly supplanting joint replacements.
For developmental biologist Karen Lyons, PhD, professor and vice chair of the research team, this project is personal.
“I have osteoarthritis, so I’m extremely motivated in translational research,” she says. “This ARPA-H-funded UCLA project has shifted my focus into finding an economically and clinically practical solution. We want something that anyone — a millionaire or an average Joe — can access.”
Dr. Lyons, whose lab studies signaling pathways causing cartilage to develop in utero, says UCLA Health is ideally positioned to carry out the level of research required by this ARPA-H-funded UCLA project. Because UCLA’s medical school and hospital are in close proximity to the basic science labs, “… we have cross-fertilization of ideas. In fact, Dr. Kremen and I share lab space. That’s unique,” she says.
Additionally, because UCLA Health is in the second largest city in the U.S. with one of the most diverse populations, it has “… the clinical infrastructure and geographic footprint to engage with many OA patients,” says Dr. Kremen.
For these reasons, UCLA Health will lead the clinical trial resulting from current research as early as 2027.
Underlying work
Participation in the NITRO program aligns with UCLA Health’s development of a longevity and anti-aging program, in part because OA is considered a disease of aging. However, ongoing research by Dr. Kremen underscores the point that increasing risk for OA may be established earlier in life. His lab is conducting a clinical trial to evaluate the use of a drug, anakinra, in people suffering a torn anterior cruciate ligament (ACL).
“We once thought ACL reconstruction would make the knee more stable and help prevent arthritis. But that’s not the case,” says Dr. Kremen. “It doesn’t prevent downstream OA from happening 10-20 years later.”
Dr. Kremen and team have tracked biomarkers occurring when an ACL is torn and have found pro-inflammatory molecules that can be targeted with anakinra, originally developed for rheumatoid arthritis.
“The theory is if we treat people early after an ACL tear and introduce a corrective molecule while the pro-inflammatory biomarker storm is going on, we can redirect those biomarkers and prevent OA down the line,” he explains.
This intervention following acute ACL injury takes advantage of a cartilage-sensitive MRI that can detect an abnormal signature on the cartilage. UCLA Health is among just a few institutions in the country that have this technology. Dr. Lyons says because Dr. Kremen has experience with clinical trials in the OA space, he brings real-life experience to the trial phase of NITRO, giving UCLA Health a strong advantage moving forward.
Powerful funding
In addition to medical research funding, this ARPA-H-funded UCLA project supports translational aspects of the undertaking, such as navigating the Food and Drug Administration process, commercializing a product when successfully identified, scaling up production and making it equitably available to the masses.
The entire project has delivered a unique opportunity to those participating.
“In my entire career, I might treat 20,000 patients and have an impact on their lives. But if we can develop a viable therapy through NITRO, it has the potential to impact millions of people — the opportunity of a lifetime,” says Dr. Kremen.
Dr. Lyons adds that NITRO allows the research team to advance ideas that might never have a chance to be evaluated otherwise.
“There are very few funding opportunities that cater to this kind of project,” she says. “If you ever find one, take it.”
Clearly, the project criteria are very challenging. “But with commitment from many talented people and resources we’ve been provided, we can push the chances for success to be in our favor,” says Dr. Kremen. “People throw around the term ‘moonshot.’ But even if we fall short of the moon, we might get a new therapy that works on Earth. We can make a difference, and in our lifetime.”