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EntreMed encouraged by rheumatoid arthritis lead compound

By Wai Lang Chu , 26-Jun-2006

EntreMed has produced hard data demonstrating antiangiogenic activity of its lead compound against the devastating effects of rheumatoid arthritis (RA). The results pave the way to developing therapeutics for the cancer and inflammatory treatment.

Scientists have been encouraged by this latest development as the next step in disease modifying antirheumatic drug (DMARD) treatment as the compound 2- methoxyestradiol (2ME2), inhibits angiogenesis, which is necessary to support the growth of the pannus.

In people suffering from rheumatoid arthritis, pannus tissue eventually forms in the joint affected by the disease, causing loss of bone and cartilage

In addition further tissue analyses on the articular joints from 2ME2-treated models demonstrated decreased von Willebrand factor expression indicating a loss or inhibition of vascularity.

In addition, RT-PCR on dissected synovial tissue showed suppression in the gene expression of the angiogenic growth factors, VEGF and FGF-2.

"These preclinical data further define the impact of 2ME2 on inflammation and disease progression and indicate that 2ME2 may represent a novel agent for the treatment of rheumatoid arthritis," said Ernest Brahn, Professor of Medicine and Rheumatology Program Director, Division of Rheumatology, University of California Los Angeles.

"The demonstration that 2ME2 inhibits angiogenesis in this model of rheumatoid arthritis now establishes a mechanistic link that leads to the involution of collagen-induced arthritis," he added.

Rheumatoid arthritis affects over 2 million US adults, of which about two-thirds of them are women. The disease characterised by pain, stiffness, swelling, and deformity can become debilitating.

Within 5 years of diagnosis, a third of patients are no longer working, and within 10 years, half of the patients have substantial functional disability. RA can shorten life expectancy by 5-10 years.

"Angiogenesis is a needed component of pannus growth in rheumatoid arthritis, and 2ME2, which has antiangiogenic properties, may represent a novel oral, non-immunologic DMARD approach to treating this disease," said EntreMed Vice President and Chief Medical Officer, Carolyn Sidor, commenting on the study results.

"We will continue to explore 2ME2's DMARD activity in preclinical rheumatoid arthritis models with the intent of supporting clinical development in RA in addition to our Phase 2 oncology program."

Rheumatoid arthritis (RA), one of the most common forms of arthritis, is a systemic disease characterised by inflammation of the membrane lining of the joint, which causes pain, stiffness, redness, swelling, and loss of function in the joint.

The inflamed joint lining, called the synovium, releases enzymes that destroy bone and cartilage, causing the joint to lose its shape and alignment. This process can result in joint pain, loss of movement, and deformity.

EntreMed presented their results at the Annual European Congress of Rheumatology EULAR 2006 being held this week in Amsterdam, The Netherlands.

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