Targeting the inflamed synovium

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Public release date: 29-Mar-2006

Contact: Amy Molnar

Targeting the inflamed synovium

Exploring the promise and imperative of tissue-specific strategies

for the treatment of rheumatoid arthritis

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 (http://

www.interscience.wiley.com/journal/arthritis), 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.

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Editorial: " Targeting the Inflamed Synovium: The Quest for

Specificity, " Toby Garrood and Costantino Pitzalis, Arthritis &

Rheumatism, April 2006, 54:4, pp. 1055-1060.

http://www.eurekalert.org/pub_releases/2006-03/jws-tti032206.php