Targeted Research Initiative in Osteoarthritis
Goal – Catalyze new treatments for Osteoarthritis
The Arthritis Foundation has set a goal of finding better ways to prevent Osteoarthritis (OA) and to minimize its impact on the 27 million Americans it affects.
Developing New Treatments
Today’s treatments for OA – joint replacement, weight loss and exercise, medication to reduce pain and inflammation – alleviate symptoms. Joint replacement surgery is not a realistic solution for the large number of people who are projected to develop OA, and exercise and weight loss alone do not restore function or provide adequate long term pain relief. Despite existing mediations and interventions, OA remains the nation’s most common cause of disability.
Development of new treatments has been hampered by several factors. OA research has lagged because the disease is often regarded as an inevitable side effect of aging, rather than a disease that could be prevented and, one day, cured.. Only recently have scientists gained an understanding of the pathophysiology of OA, and that the disease affects multiple tissues of the joint. Past studies in OA have often focused on older patients with advanced disease, resulting in treatments that work for only some patients. Finally, FDA rules make it difficult for pharmaceutical companies to develop OA-specific medications.
Two things are needed to develop new and effective treatments:
The ability to detect the OA disease process prior to the onset of symptoms;
Medical intervention to slow or stop the OA disease process and permit the joint to heal.
There are many forms of OA and each responds differently to specific treatments. To advance the understanding of OA, scientists must focus on specific forms of OA and develop disease predictors to allow prevention and early diagnosis.
The Anterior Cruciate Ligament Injury Model
The Arthritis Foundation believes that progress can be made by focusing research on joints that have sustained trauma. An ideal model is represented by young athletes who sustain an acute injury to the anterior cruciate ligament (ACL) in the knee. At the time of injury, cells within the cartilage of the knee die and the molecules found outside the cartilage cells, which provide for its strength and elasticity, begin to break down. This molecular degradation continues to weaken cartilage for years after the injury and the cartilage eventually loses the ability to sustain itself as the body goes through its normal activities. As a result, more than half of patients with acute ACL injuries develop severe OA within 10 to 15 years. Because the pathological processes that take place in the injured knee are very similar to those that lead to OA in the general population, a treatment that stabilizes the cartilage in the months following the injury could benefit all OA patients.
Important advantages of focusing on the ACL injury model include:
This approach can determine the precise time when the disease process begins;
Scientists can study the pathogenic mechanisms as they begin in initially healthy tissues and observe how these processes lead to cartilage breakdown, bone proliferation, and synovial inflammation;
Investigators have access to the affected tissue since many patients with joint trauma undergo surgical repair;
Post-traumatic OA progresses over a relatively short time, a fact of great importance to drug development;
ACL injury in humans is closely related to many to animal models of OA, allowing scientisit to learn from both animal and patient based research.
The Arthritis Foundation will bring together basic biomedical scientists, rheumatologists, radiologists, and orthopedic surgeons in a collaborative effort to understand the mechanisms of post-traumatic OA and to find ways to improve the outcome either through medical or surgical treatments.
Expected Outcomes
We expect that research based on this model will lead to:
• Faster drug development. This model offers a way to test new drug therapies in relatively short time frames, as opposed to the present FDA outcome measure requiring alteration in bone structure on x-rays (something that could require years or a decade).
• Development of new diagnostic tests for very early OA. Scientist have devised a broad array of biochemical, immunological, and imaging tests that detect the breakdown of the cartilage matrix. Further research will help refine and validate these tests and could provide a way to detect OA before symptoms begin.
• Existing drug therapies could be applied to OA treatment and prevention. If the FDA agrees that stabilizing cartilage after knee injury is an acceptable measure of treatment, it is possible that existing drug therapies could be brought to market specifically for the treatment of OA.
How You Can Help
The Arthritis Foundation is reviewing grant applications for research that will
Help us gain a better understanding of post-traumatic OA;
Use the post-traumatic OA model to develop better biochemical or imaging-based bio-markers for OA;
Identify strategies to improve the outcome of post-traumatic OA through medical, physical therapy, or surgical means. We are also seeking to open the door for large scale clinical trials of existing agents as interventions in patients with acute ACL injuries.
The Arthritis Foundation hopes to fund $25 million over the next 5 years toward this important research initiative. Your support will help fund fellowships, innovative research grant and strategic research partnerships to bring us closer to more effective treatments and, ultimately, a cure for osteoarthritis.
