DURHAM, N.C. – Duke Health is part of a multi-institution research team receiving federal Advanced Research Projects Agency for Health (ARPA-H) funding to develop an osteoarthritis treatment that regenerates joints.
The research project, which includes teams from Boston Children’s Hospital and the David Geffen School of Medicine at UCLA, was awarded a contract of up to $33 million, funded in two phases over five years. The project director is Benjamin Alman, M.D., chair of the Department of Orthopaedic Surgery at Duke University School of Medicine.
“We need a new approach to treating osteoarthritis, which is a leading cause of disability and represents a $128 billion cost burden on the U.S. health care system,” Alman said. “Regenerating cartilage and bone would be an effective therapy, and we have the technology, resources, and expertise to make this a reality.”
The research team will base its new therapy on recent evidence that joint tissues can heal. They will build on previous findings from project members, including the identification of small molecules and proteins that improve the cartilage regeneration process, the development of methods to deliver agents and target them to relevant joint tissues, the restoration of joint and bone tissue to a more standard “younger” state in animal studies; and an understanding of the genes and pathways needed to generate articular cartilage.
“We will achieve our goal of delivering a regenerative treatment for osteoarthritis by capitalizing on the expertise of our multi-site team, which includes biologists with extensive experience in bone and cartilage regeneration, as well as chemists and bioengineers with expertise in cutting-edge technologies to deliver therapeutic agents to the right place at the right time,” said Thomas Kremen, M.D., orthopaedic surgeon at UCLA Health and lead investigator for the planned clinical trial.
The researchers propose three therapies. The first would be an injection targeted into the joint to release regenerative factors in the bone supporting injured cartilage. The second would be an injection into the joint to regenerate cartilage tissue. A third therapy would be a systemic version of the injectable that could home in on diseased cartilage tissues in patients who have osteoarthritis in multiple joints.
By applying these therapies to specific cell populations over the appropriate time frame, the researchers hope to rebuild and rejuvenate a fully functional joint.
“Our team represents a collective and relentless effort to deliver a solution to those that suffer from joint pain,” said April Craft, Ph.D., assistant professor of orthopedic surgery at Boston Children's Hospital and Harvard Medical School and site director of the research project. “Our goal is to restore function to damaged joints by reactivating our cells in a way that promotes healthy tissue regeneration.”
The researchers will collaborate across a centrally coordinated process to share findings quickly and capitalize on the diverse expertise within the team. Work will include developing pre-clinical large animal studies, planning for clinical trials with a diverse population of participants, and drafting an effective commercialization and technology transfer plan.
“A unique aspect of the work is considering the diversity of patients who would benefit from the treatment from the start of the project,” Alman said. “Osteoarthritis does not affect all populations equally, and the project will include an arm to identify populations that would benefit the most and to ensure that the proposed therapies are readily available to those patients.”
Funding is through ARPA-H's Novel Innovations for Tissue Regeneration in Osteoarthritis (NITRO) program. Its goal is to develop new ways to promote joint repair, including injectables that regenerate bones and cartilage and replacement joints built from human cells.
ARPA-H is a federal agency established to advance high-potential, high-impact biomedical and health research that cannot be readily accomplished through traditional research or commercial activity.