$33 Million to Truly Regenerate Arthritic Joints

Duke School of Medicine, Boston Children’s Hospital, and University of California Los Angeles (UCLA) have been awarded a contract of up to $33 million from the Advanced Research Projects Agency for Health to develop an osteoarthritis treatment that is not only disease modifying but will also regenerate joints.

Benjamin Alman, M.D., chair of the Department of Orthopaedic Surgery at Duke University School of Medicine and director of the project, stated, “We need a new approach to treat osteoarthritis, which is a leading cause of disability and represents a $128 billion cost burden on the U.S. health care system. Regenerating cartilage and bone would be an effective therapy, and we have the technology, resources, and expertise in hand to make this a reality.”

Working from recent evidence that joint tissues can heal, the researchers say they will build on previous findings such as “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 normal ‘younger’ state in animal studies; and an understanding of the genes and pathways needed to generate articular cartilage.”

When OTW asked for details on these small molecules and proteins, Dr. Alman commented, “These agents were selected because there is evidence that they will help cells in arthritic joints regrow and will be safe to use in patients. This is a time release method that will allow each small molecule or protein to be delivered at just the right time. They are also selected to also be safe and cost effective.”

“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., orthopedic surgeon at UCLA Health and lead investigator for the planned clinical trial.

The researchers propose three therapies.

1. The first would be an injection targeted into the joint to release regenerative factors in the bone supporting injured cartilage.
2. The second would be an injection into the joint to regenerate cartilage tissue.
3. 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.

The first of the three proposed therapies would be an injection targeted into the joint to release regenerative factors in the bone supporting injured cartilage. The second treatment involves 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 own cells in a way that promotes healthy tissue regeneration.”

“A unique aspect of the work is considering the diversity of patients who would benefit from the treatment from the start of the project,” Dr. 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.”

“The program aims to develop treatments that can be tried in patients within five years,” stated Dr. Alman to OTW.