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Introduction

Immunology 101: Pathways to a Cure  

Evolving Concepts of RA: Progressing from Bench to Bedside

Cutting Edge Biotechnology Advances

Paving the Way for Patient-specific Therapy

Early Detection and Monitoring of OA

New Cartilage for Damaged Joints

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Cutting Edge Biotechnology Advances  

Imagine a time when treatment for RA is specially designed for each patient… or an imaging or blood test can detect early signs of cartilage or bone damage before disease symptoms occur so further damage can be prevented… or those who already have significant joint damage are able to get a cartilage transplant using tissue that had been engineered in the laboratory, instead of having to resort to surgery. Sound like pipe dreams? Not so, say several conference presenters. 

Paving the Way for Patient-specific Therapy
A therapy that selectively targets the specific proteins that provoke the abnormal immune response in RA would be safer and more effective than traditional immunosuppressive drugs. Previously, scientists have been unable to determine which proteins are attacked in RA. However, as described in presentations by Stanford researchers, Paul J. Utz, MD and Bill Robinson, MD, PhD, significant progress has been made towards identifying some of the culprit proteins. The investigators utilized a new technology called "microarrays," which consist of glass slides dotted by a robotic device with over 2,300 proteins and other molecules that could be attacked in arthritis and related conditions. Then they applied blood taken from patients with RA, osteoarthritis, reactive arthritis and lupus and analyzed the results to see which molecules were attacked more often in RA as compared to the other diseases. In a recently published study, these researchers have shown in mice with a disease that resembles multiple sclerosis that this technology can be used to develop a specialized vaccine that successfully turned off the immune response. Read more... 

What's the relevance to people with arthritis? Microarray technology may soon be able to direct the design of patient-specific treatments, which would target just those proteins that cause tissue damage, or perhaps even a specific vaccine for diseases that would prevent or even cure arthritis.



Early Detection and Monitoring of OA
By the time that osteoarthritis (OA) is diagnosed, pain and irreparable cartilage damage are often already present. However, much progress is being made in developing efficient methods for detecting early changes in the joint and for monitoring the progression of the disease. For instance, Mark Markel, DVM, PhD and his colleagues at the University of Wisconsin in Madison are using an animal model of OA in which dogs develop arthritis of the hip to study the value of two antibody tests. Developed to detect cartilage breakdown products, these antibodies were found to be good tools to predict the development of OA in these animals. Use of markers such as these to predict the progression of OA in its early stages in humans might help guide preventative measures and options for therapies. 

Using another approach, Peter Hardy, PhD, of the University of Kentucky, has been following patients with varying degrees of OA and comparing data obtained from MRIs (magnetic resonance imaging) to X-ray data. The MRIs map the thickness of the cartilage as well as the narrowing of the joints as the arthritis progresses. This appears to be a more sensitive tool than X-rays for evaluating the progression of joint damage in OA and the effectiveness of different therapies.

What's the relevance to people with arthritis? New biomarker and imaging tests are providing a more sensitive picture of how OA progresses. Eventually, they will allow doctors to detect early signs of OA so that further damage can be prevented. Such tools will also aid in the discovery and testing of new therapies.

New Cartilage for Damaged Joints
An exciting area in biotechnology is "tissue engineering," using live cells to rebuild damaged tissue. It is difficult to grow high-quality cartilage that maintains the smooth, shock-absorbing function of natural cartilage. Jennifer Elisseeff, PhD at Johns Hopkins University and her colleagues have determined that there are different layers or zones within normal cartilage and that cartilage cells have different biologic properties depending on which zone they are located in. She reported data that showed that they could obtain and grow cartilage from the different zones, maintaining the unique properties of the cartilage cells from each zone. 

Similarly, Jean F. Welter, MD, PhD, at Case Western Reserve University, reported progress in his work on growing cartilage cells in the laboratory. His laboratory is using undeveloped "stem cells" taken from the bone marrow that are applied in different ways to a sponge-type scaffold which holds them together while they develop into cartilage tissue. The cartilage tissue is grown within a special device called a bioreactor, which allows for Dr. Welter's group to continuously monitor and determine the optimal set of conditions for successfully engineering high-quality cartilage.

What's the relevance to people with arthritis? If successful, these studies will provide another approach to repair cartilage damaged by OA and could form the basis for the development of a new generation of treatments that provide an alternative to joint replacement surgery for those with severe joint damage.

 

Research Update is compiled by Michele Boutaugh, BSN, MPH, Medical and Scientific Affairs Department, National Office.

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