ARRA Investments in Osteoarthritis
Public Health Burden
Osteoarthritis (OA) is the most common form of arthritis and the major cause of physical disability in older people. An estimated 12.1 percent of the U.S. population (nearly 27 million Americans) age 25 and older have OA. By 2030, about 72 million Americans will have passed their 65th birthday and will be at high risk for the disease.
Measuring Tissue Integrity
A degenerative disease, OA involves the whole joint: the cartilage (the hard but slippery tissue that covers the ends of bones), the ligaments and other soft tissues around a joint (such as the meniscus that cushions the knee), and even the bones themselves. Several groups of investigators are using ARRA funds to develop non-invasive methods to evaluate healing after a joint injury or cartilage deterioration during OA development and progression. Projects include:
Developing an imaging technique that clinicians can use to monitor torn menisci in injured knees and advise patients about when they can safely resume activities
. At present, physicians do not have an accurate way of determining when a patient has healed completely, and patients can reinjure themselves if they stress the injured tissue before it has fully recovered.
Assessing the structural and functional integrity of cartilage using magnetic resonance imaging (MRI)
. Clinicians currently rely on x rays to monitor joint damage, but the findings do not necessarily relate to OA symptoms. And, unlike MRI, x rays are not sensitive enough to test new drugs that might block joint degradation.
Discovering and Testing Treatments
At present, OA drug therapies relieve pain, but do not halt joint degeneration and disease progression. Even surgeries to repair torn ligaments and other soft tissues of an injured joint fail to prevent post-traumatic OA. Whether damaged by accident or through normal activities, cartilage does not heal well. Therefore, researchers are exploring a multipronged approach to prevent OA from developing and to slow its progression if it occurs. Through ARRA, they are:
Developing new drugs that could prevent post-traumatic OA
or repair the small cracks in cartilage that signal OA onset
Establishing a collection of mouse models that researchers can use to identify the genes that contribute to cartilage healing
. Once scientists understand what genes are involved, they may be able to develop drugs that can block OA by repairing cartilage or halting its degradation.
Exploring how movement and weight-bearing activity influence the formation of cartilage and meniscal tissues
. Knowledge of how mechanical stresses affect tissue development has the potential to guide the development of functional tissue replacements and may explain the success or failure of different tissue engineering strategies.
Testing promising approaches for repairing damaged cartilage in large animals before beginning clinical trials
Identifying tissue banking and cartilage storage technology that will improve the usefulness of cartilage transplants for people who have severe joint damage
. At present, the number of people who benefit from cartilage transplants is limited by a lack of fresh donor cartilage. The ability to store cartilage for future procedures would allow more people to be treated.
Determining which molecules in the synovial fluid that lubricates the knee joint are important for joint health or OA progression.
If researchers understood how the fluid influences normal and impaired joint functioning, they might be able to develop therapies that slow or halt OA by manipulating its composition.
Studying how the menisci attach to the leg bones that comprise the knee. Understanding the structure and composition of meniscal attachments will help investigators design replacement tissues that can prevent or reduce the burden of knee OA.
Assessing OA Risk
People can reduce their risk of developing OA if they maintain a healthy weight, exercise regularly, and do not smoke. As researchers develop additional interventions to prevent OA onset or slow its progression, the ability to identify people who will benefit most from these new therapies will become even more important. ARRA-funded researchers are exploring ways to identify at-risk people by:
Finding genetic alterations that increase susceptibility to knee OA
. The discovery of genetic variants that protect against or increase a person’s risk of developing OA is likely to suggest targets for the development of disease modifying agents. Moreover, investigators could use genetic markers to identify appropriate participants for clinical trials.
Discovering proteins or other substances in the blood or urine that indicate cartilage damage or repair following an injury
. The ability to monitor patients’ recovery with markers of post-traumatic OA could guide physical therapy regimens for patients. Integrating the markers into clinical trials of drugs to promote healing and prevent OA also could improve studies’ efficiency.
Lawrence RC, et al., Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II.
-- Evaluation of an MRI Biomarker for Meniscal Repair -- Potter, Hollis G. (NY)
-- Multiparametric MRI of Cartilage -- Burstein, Deborah (MA)
-- In Vivo Early Detection of Cartilage Degeneration Using High Field MRI -- Li, Xiaojuan (CA)
-- Treatment of posttraumatic arthritis and prevention of osteoarthritis -- Lotz, Martin K. (CA)
-- A novel therapeutic target for OA that restores IGF-1 responses -- Moore, Emma E. (WA)
-- Multicenter Cartilage Repair Preclinical Trial in Horses -- Chu, Constance R. (PA)
-- Genetic Mouse Models of Cartilage Healing -- Sandell, Linda J. (MO)
-- Modulation of MSC Differentiation for Fibrocartilage Tissue Engineering -- Levenston, Marc (CA)
-- Enabling ACL Repair Using Proprietary Collagen Device -- Sandoski, Aaron (MA)
-- Biologically Enhanced Healing of Autograft ACL Reconstruction -- Fleming, Braden C. (RI)
-- Gene therapeutic approaches to cartilage repair -- Goodrich, Laurie (CO)
-- In Vivo Performance of Osteochondral Allografts -- Bugbee, William D. (CA)
-- Mechanisms of Articular Cartilage Lubrication -- Sah, Robert L. (CA)
-- Structure and Function of Meniscal Horn Attachments -- Haut Donahue, Tammy Lynn (MI)
-- Genome-wide Association Study to Identify Genetic Components of Knee OA: The OAI -- Jackson, Rebecca D. (OH)
-- Serum microRNAs as biomarkers of post-traumatic osteoarthritis -- Gibson, Gary J. (MI)
-- Biomarkers of the risk for post-traumatic osteoarthritis -- Martin, James A. (IA)
Page Last Updated on June 30, 2018
Turning Discovery Into Health