Targeting the inflamed synovium: The quest for specificity

Rheumatoid arthritis (RA) is a complex and destructive inflammatory disease.

Despite recent impressive advances in disease-modifying antirheumatic drugs and biologic therapies, treatment is not always effective and still has many safety ramifications. Assessment of RA, once dependent on X-ray measurement of cartilage and bone destruction, has also experienced dramatic gains with the use of magnetic resonance imaging and ultrasound. Still, accurate early detection and monitoring of short-term changes in simultaneous joints remains elusive.

To further improve the delivery of both drugs and imaging agents for the treatment of RA, researchers are increasingly focusing on the inflamed tissue that leads to joint destruction!Xthe synovium. In the April 2006 issue of Arthritis & Rheumatism, noted rheumatology specialists with Kings College London, Dr. Toby Garrood and Dr. Costantino Pitzalis offer an overview of recent breakthroughs and a preview of future directions in this critical quest for specificity.

Among important and promising research, the authors discuss:

• Liposome technology, the creation of microscopic vesicles for improved tissue delivery of therapeutic compounds. Liposomes have been successfully used in the imaging of inflamed joints, as well as in dispensing drugs to RA patients. In one animal model experiment, liposome-encapsulated prednisolone was reported to achieve the effects equivalent to 10-fold higher doses of the free drug.
• Specific targeting of liposomes to inflamed cells in the synovium. In a novel experiment with a rat model, corticosteroids were encapsulated in RGD peptide liposomes targeted to bind to inflamed cells in the walls of blood vessels. The steroid treatment was delivered rapidly and worked effectively to reduce synovial inflammation, with no signs of the conventional side effects.
• Further potential targets within the inflamed joint, including synovial macrophages, cells that work to remove harmful bacteria, and E-selectin, an adhesion molecule in the blood vessel walls that recruits immune-boosting lymphocytes.

Looking forward, Dr. Garrood and Dr. Pitzalis highlight substantial, indirect evidence of the existence of a truly specific synovial homing receptor "the key to unlocking the mechanisms of inflammation" and exciting advances in phage display technology. "Significant progress is being made in the development of technologies for specific targeting of the synovium and delivery of therapeutic agents," the authors attest. They conclude by emphasizing the importance of identifying novel molecular targets within the synovium for optimizing the diagnosis and management of RA.